Publications by authors named "Devin B Phillips"

31 Publications

Ventilation/Perfusion Mismatch: A Novel Target for COPD Treatment.

Chest 2022 Apr 4. Epub 2022 Apr 4.

Respiratory Investigation Unit, Division of Respiratory and Critical Care Medicine, Department of Medicine, Queen's University and Kingston Health Sciences Centre, Kingston, Ontario, Canada.

In people with chronic obstructive pulmonary disease (COPD), pulmonary gas-exchange efficiency may be impaired due to abnormal alveolar ventilation (VA) and/or capillary perfusion (Qc), both of which have been reported in early and mild stages of the disease. Such abnormalities often accompany significant clinical consequences such as activity-related dyspnea and exercise intolerance. Although much attention has been paid to pharmacological treatment of mechanical abnormalities (e.g., bronchodilators to deflate the lungs) in COPD, increasing neurochemical afferent activity, secondary to gas-exchange inefficiency, has remained elusive as a therapeutic target. Hence, in this invited review, we first summarize how dyspnea, leading to poor exercise tolerance in COPD may be explained by an increased venous admixture due to low VA/Qc and/or wasted ventilation related to high VA/Qc. We review the conflicting evidence supporting current treatments for gas-exchange inefficiency and exercise tolerance which act primarily on VA (bronchodilators, anti-inflammatory medications) or Qc (oral and inhaled vasodilators, almitrine and supplemental oxygen). Finally, to address the current knowledge and health-care gaps, we propose two independent clinical research foci that may lead to a better understanding of the role of pulmonary gas-exchange efficiency and activity-related dyspnea in COPD: 1) improved and deeper phenotyping of COPD patients with VA/Qc abnormalities, and, 2) evaluation of existing and novel pharmacological treatments in relation to improved gas-exchange inefficiency, exertional dyspnea, and exercise tolerance across the spectrum of COPD severity.
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http://dx.doi.org/10.1016/j.chest.2022.03.033DOI Listing
April 2022

Impaired Ventilatory Efficiency, Dyspnea and Exercise Intolerance in Chronic Obstructive Pulmonary Disease: Results from the CanCOLD Study.

Am J Respir Crit Care Med 2022 Mar 25. Epub 2022 Mar 25.

Queen's University, Division of Respiratory and Critical Care Medicine, Department of Medicine, Kingston, Ontario, Canada;

Rationale: Impaired exercise ventilatory efficiency (high ventilatory requirements for CO2 [V̇E/V̇CO2]) provides an indication of pulmonary gas exchange abnormalities in chronic obstructive pulmonary disease (COPD).

Objectives: To determine: 1) the association between high V̇E/V̇CO2 and clinical outcomes (dyspnea and exercise capacity) and its relationship to lung function and structural radiographic abnormalities; and 2) its prevalence in a large population-based cohort.

Methods: Participants were recruited randomly from the population and underwent clinical evaluation, pulmonary function, cardiopulmonary exercise testing and chest computed tomography (CT). Impaired exercise ventilatory efficiency was defined by a nadir V̇E/V̇CO2 above the upper limit of normal (V̇E/V̇CO2>ULN), using population-based normative values.

Measurements And Main Results: Participants included 445 never-smokers, 381 ever-smokers without airflow obstruction, 224 with GOLD 1 COPD, and 200 with GOLD 2-4 COPD. Participants with V̇E/V̇CO2>ULN were more likely to have activity-related dyspnea (Medical Research Council dyspnea scale≥2, odds ratio=1.77[1.31-2.39]) and abnormally low peak oxygen uptake (V̇O2peakULN was 24% in COPD (similar in GOLD 1 and 2-4), which was greater than in never-smokers (13%) and ever-smokers (12%).

Conclusions: V̇E/V̇CO2>ULN was associated with greater dyspnea and low VO2peak and was present in 24% of all participants with COPD, regardless of GOLD stage. The results show the importance of recognizing impaired exercise ventilatory efficiency as a potential contributor to dyspnea and exercise limitation, even in mild COPD.
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http://dx.doi.org/10.1164/rccm.202109-2171OCDOI Listing
March 2022

Inhaled nitric oxide does not improve maximal oxygen consumption in endurance trained and untrained healthy individuals.

Eur J Appl Physiol 2022 Mar 22;122(3):703-715. Epub 2022 Jan 22.

Division of Pulmonary Medicine, Faculty of Medicine and Dentistry, University of Alberta, 3-135 Clinical Sciences Building 8440 112 St NW, Edmonton, AB, T6G 2B7, Canada.

Purpose: Previous work suggests that endurance-trained athletes have superior pulmonary vasculature function as compared to untrained individuals, which may contribute to their greater maximal oxygen uptake ([Formula: see text]O). Inhaled nitric oxide (iNO) reduces pulmonary vascular resistance in healthy individuals, which could translate into greater cardiac output and improved [Formula: see text]O, particularly in untrained individuals. The purpose of the study was to examine whether iNO improved [Formula: see text]O in endurance trained and untrained individuals.

Methods: Sixteen endurance-trained and sixteen untrained individuals with normal lung function completed this randomized double-blind cross-over study over four sessions. Experimental cardiopulmonary exercise tests were completed while breathing either normoxia (placebo) or 40 ppm of iNO, on separate days (order randomized). On an additional day, echocardiography was used to determine pulmonary artery systolic pressure at rest and during sub-maximal exercise (60 Watts) while participants breathed normoxia or iNO.

Results: Right ventricular systolic pressure was significantly reduced by iNO during exercise (Placebo: 34 ± 7 vs. iNO: 32 ± 7; p = 0.04). [Formula: see text]O was greater in the endurance trained group (Untrained: 3.1 ± 0.7 vs. Endurance: 4.3 ± 0.9 L min; p < 0.01), however, there was no effect of condition (p = 0.79) and no group by condition interaction (p = 0.68). Peak cardiac output was also unchanged by iNO in either group.

Conclusion: Despite a reduction in right ventricular systolic pressure, the lack of change in [Formula: see text]O with iNO suggests that the pulmonary vasculature does not limit [Formula: see text]O in young healthy individuals, regardless of fitness level.
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http://dx.doi.org/10.1007/s00421-021-04866-3DOI Listing
March 2022

Compensatory responses to increased mechanical abnormalities in COPD during sleep.

Eur J Appl Physiol 2022 Mar 16;122(3):663-676. Epub 2022 Jan 16.

Department of Medicine, Queen's University, Kingston, Canada.

Purpose: To assess whether night-time increases in mechanical loading negatively impact respiratory muscle function in COPD and whether compensatory increases in inspiratory neural drive (IND) are adequate to stabilize ventilatory output and arterial oxygen saturation, especially during sleep when wakefulness drive is withdrawn.

Methods: 21 patients with moderate-to-severe COPD and 20 age-/sex-matched healthy controls (CTRL) participated in a prospective, cross-sectional, one-night study to assess the impact of COPD on serial awake, supine inspiratory capacity (IC) measurements and continuous dynamic respiratory muscle function (esophageal manometry) and IND (diaphragm electromyography, EMGdi) in supine sleep.

Results: Supine inspiratory effort and EMGdi were consistently twice as high in COPD versus CTRL (p < 0.05). Despite overnight increases in awake total airways resistance and dynamic lung hyperinflation in COPD (p < 0.05; not in CTRL), elevated awake EMGdi and respiratory effort were unaltered in COPD overnight. At sleep onset (non-rapid eye movement sleep, N2), EMGdi was decreased versus wakefulness in COPD (- 43 ± 36%; p < 0.05) while unaffected in CTRL (p = 0.11); however, respiratory effort and arterial oxygen saturation (SpO) were unchanged. Similarly, in rapid eye movement (stage R), sleep EMGdi was decreased (- 38 ± 32%, p < 0.05) versus wakefulness in COPD, with preserved respiratory effort and minor (2%) reduction in SpO.

Conclusions: Despite progressive mechanical loading overnight and marked decreases in wakefulness drive, inspiratory effort and SpO were well maintained during sleep in COPD. Preserved high inspiratory effort during sleep, despite reduced EMGdi, suggests continued (or increased) efferent activation of extra-diaphragmatic muscles, even in stage R sleep.

Clinical Trial Information: The COPD data reported herein were secondary data (Placebo arm only) obtained through the following Clinical Trial: "Effect of Aclidinium/Formoterol on Nighttime Lung Function and Morning Symptoms in Chronic Obstructive Pulmonary Disease" ( https://clinicaltrials.gov/ct2/show/NCT02429765 ; NCT02429765).
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http://dx.doi.org/10.1007/s00421-021-04869-0DOI Listing
March 2022

Qualitative Components of Dyspnea during Incremental Exercise across the COPD Continuum.

Med Sci Sports Exerc 2021 12;53(12):2467-2476

Respiratory Investigation Unit, Department of Medicine, Queen's University and Kingston Health Sciences Centre, Kingston General Hospital Campus, Kingston, Ontario, CANADA.

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.
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http://dx.doi.org/10.1249/MSS.0000000000002741DOI Listing
December 2021

Exertional ventilation/carbon dioxide output relationship in COPD: from physiological mechanisms to clinical applications.

Eur Respir Rev 2021 Sep 15;30(161). Epub 2021 Sep 15.

Respiratory Investigation Unit and Laboratory of Clinical Exercise Physiology, Queen's University and Kingston General Hospital, Kingston, ON, Canada.

There is well established evidence that the minute ventilation (')/carbon dioxide output (' ) relationship is relevant to a number of patient-related outcomes in COPD. In most circumstances, an increased '/' reflects an enlarged physiological dead space ("wasted" ventilation), although alveolar hyperventilation (largely due to increased chemosensitivity) may play an adjunct role, particularly in patients with coexistent cardiovascular disease. The '/' nadir, in particular, has been found to be an important predictor of dyspnoea and poor exercise tolerance, even in patients with largely preserved forced expiratory volume in 1 s. As the disease progresses, a high nadir might help to unravel the cause of disproportionate breathlessness. When analysed in association with measurements of dynamic inspiratory constraints, a high '/' is valuable to ascertain a role for the "lungs" in limiting dyspnoeic patients. Regardless of disease severity, cardiocirculatory (heart failure and pulmonary hypertension) and respiratory (lung fibrosis) comorbidities can further increase '/' A high '/' is a predictor of poor outcome in lung resection surgery, adding value to resting lung hyperinflation in predicting all-cause and respiratory mortality across the spectrum of disease severity. Considering its potential usefulness, the '/' should be valued in the clinical management of patients with COPD.
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http://dx.doi.org/10.1183/16000617.0190-2020DOI Listing
September 2021

Mechanisms of Exertional Dyspnea in Patients with Mild COPD and a Low Resting DL.

COPD 2021 10 8;18(5):501-510. Epub 2021 Sep 8.

Respiratory Investigation Unit, Department of Medicine, Queen's University, and Kingston Health Sciences Centre, Kingston, Ontario, Canada.

Patients with mild chronic obstructive pulmonary disease (COPD) and lower resting diffusing capacity for carbon monoxide (DL) often report troublesome dyspnea during exercise although the mechanisms are not clear. We postulated that in such individuals, exertional dyspnea is linked to relatively high inspiratory neural drive (IND) due, in part, to the effects of reduced ventilatory efficiency. This cross-sectional study included 28 patients with GOLD I COPD stratified into two groups with ( = 15) and without ( = 13) DL less than the lower limit of normal (
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http://dx.doi.org/10.1080/15412555.2021.1932782DOI Listing
October 2021

Ventilatory efficiency in athletes, asthma and obesity.

Eur Respir Rev 2021 Sep 20;30(161). Epub 2021 Jul 20.

Division of Pulmonary Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.

During submaximal exercise, minute ventilation ( ) increases in proportion to metabolic rate ( carbon dioxide production ( )) to maintain arterial blood gas homeostasis. The ratio / , commonly termed ventilatory efficiency, is a useful tool to evaluate exercise responses in healthy individuals and patients with chronic disease. Emerging research has shown abnormal ventilatory responses to exercise (either elevated or blunted / ) in some chronic respiratory and cardiovascular conditions. This review will briefly provide an overview of the physiology of ventilatory efficiency, before describing the ventilatory responses to exercise in healthy trained endurance athletes, patients with asthma, and patients with obesity. During submaximal exercise, the / response is generally normal in endurance-trained individuals, patients with asthma and patients with obesity. However, in endurance-trained individuals, asthmatics who demonstrate exercise induced-bronchoconstriction, and morbidly obese individuals, the / can be blunted at maximal exercise, likely because of mechanical ventilatory constraint.
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http://dx.doi.org/10.1183/16000617.0206-2020DOI Listing
September 2021

Reduced exercise tolerance in mild chronic obstructive pulmonary disease: The contribution of combined abnormalities of diffusing capacity for carbon monoxide and ventilatory efficiency.

Respirology 2021 08 7;26(8):786-795. Epub 2021 Apr 7.

Respiratory Investigation Unit, Department of Medicine, Queen's University and Kingston Health Sciences Centre, Kingston General Hospital Campus, Kingston, Ontario, Canada.

Background And Objective: The combination of both reduced resting diffusing capacity of the lung for carbon monoxide (DL ) and ventilatory efficiency (increased ventilatory requirement for CO clearance [V˙ /V˙CO ]) 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 DL 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˙ /V˙CO , 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 DL at or greater than the lower limit of normal (≥LLN; Global Lung Function Initiative reference equations [n = 44]) or (2) below the
Results: Spirometry and resting lung volumes were similar in the two COPD groups. During exercise, V˙ /V˙CO (nadir and slope) was consistently higher in the DL  < LLN compared with the other groups (all p < 0.05). The DL  < LLN group had lower IRV and greater dyspnoea intensity at standardized submaximal work rates and lower peak work rate and oxygen uptake than the other two groups (all p < 0.05).

Conclusion: Reduced exercise capacity in patients with DL  < LLN was related to higher ventilatory requirements, a faster rate of decline in dynamic IRV and greater dyspnoea during exercise. These simple measurements should be considered for the clinical evaluation of unexplained exercise intolerance in individuals with ostensibly mild COPD.
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http://dx.doi.org/10.1111/resp.14045DOI Listing
August 2021

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

Front Physiol 2021 18;12:552000. Epub 2021 Mar 18.

Laboratory of Clinical Exercise Physiology and Respiratory Investigation Unit, Queen's University and Kingston General Hospital, Kingston, ON, Canada.

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 (V̇O) despite a low peak WR. Among the determinants of V̇O, only heart rate is measured during non-invasive CPET. It follows that in the absence of findings suggestive of severe impairment in O 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) PO 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.
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http://dx.doi.org/10.3389/fphys.2021.552000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012894PMC
March 2021

Blunted sympathetic neurovascular transduction is associated to the severity of obstructive sleep apnea.

Clin Auton Res 2021 06 9;31(3):443-451. Epub 2021 Feb 9.

Neurovascular Health Lab, Faculty of Kinesiology, Sport, & Recreation, University of Alberta, 1-059D Li Ka Shing Centre for Health Research Innovation, Edmonton, T6G 2E1, Canada.

Purpose: Obstructive sleep apnea (OSA) is a common disorder (~ 4%) that augments sympathetic nerve activity (SNA) and elevates blood pressure. The relationship between sympathetic vasomotor outflow and vascular responsiveness, termed sympathetic neurovascular transduction (sNVT), has been sparsely characterized in patients with OSA. Therefore, we sought to quantify spontaneous sympathetic bursts and related changes in diastolic pressure.

Methods: Twelve participants with variable severities of OSA were recruited. We collected muscle sympathetic nerve activity (MSNA) (microneurography) and beat-by-beat diastolic pressure (finger photoplethysmography) during normoxia (FiO = 0.21) and hyperoxia (FiO = 1.0) to decrease MSNA burst frequency. MSNA burst sequences (i.e. singlets, doublets, triplets and quadruplets) were identified and coupled to changes in diastolic pressure over 15 cardiac cycles as an index of sNVT. sNVT slope for each individual was calculated from the slope of the relationship between peak responses in outcome plotted against normalized burst amplitude.

Results: sNVT slope was unchanged during hyperoxia compared to normoxia (normoxia 0.0024 ± 0.0011 Δ mmHg total activity [a.u.] vs. hyperoxia 0.0029 ± 0.00098 Δ mmHg total activity [a.u.]; p = 0.14). sNVT slope was inversely associated with burst frequency during hyperoxia (r = -0.58; p = 0.04), but not normoxia (r = -0.11; p = 0.71). sNVT slope was inversely associated with the apnea-hypopnea index (AHI) (r = -0.62; p = 0.030), but not after age was considered.

Conclusions: We have demonstrated that the prevailing MSNA frequency is unmatched to the level of sNVT, and this can be altered by acute hyperoxia.
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http://dx.doi.org/10.1007/s10286-021-00784-8DOI Listing
June 2021

Inhaled nitric oxide improves ventilatory efficiency and exercise capacity in patients with mild COPD: A randomized-control cross-over trial.

J Physiol 2021 03 25;599(5):1665-1683. Epub 2021 Jan 25.

Division of Pulmonary Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

Key Points: Patients with mild chronic obstructive pulmonary disease (COPD) have an elevated ventilatory equivalent to CO production ( / ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. Despite emerging evidence that mild COPD is associated with pulmonary microvascular dysfunction, limited research has focused on experimentally modulating the pulmonary microvasculature during exercise in mild COPD. The present study sought to examine the effect of inhaled nitric oxide (iNO), a selective pulmonary vasodilator, on / , dyspnoea and exercise capacity in patients with mild COPD. Experimental iNO increased peak oxygen uptake in mild COPD, secondary to reduced / and dyspnoea. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD.

Abstract: Patients with mild chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory response to exercise, contributing to dyspnoea and exercise intolerance. Previous research in mild COPD has demonstrated an elevated ventilatory equivalent to CO production ( / ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. The present study tested the hypothesis that inhaled nitric oxide (iNO), a selective pulmonary vasodilator, would lower / and dyspnoea, and improve exercise capacity in patients with mild COPD. In this multigroup randomized-control cross-over study, 15 patients with mild COPD (FEV = 89 ± 11% predicted) and 15 healthy controls completed symptom-limited cardiopulmonary exercise tests while breathing normoxic gas or 40 ppm iNO. Compared with placebo, iNO significantly increased peak oxygen uptake (1.80 ± 0.14 vs. 1.53 ± 0.10 L·min , P < 0.001) in COPD, whereas no effect was observed in controls. At an equivalent work rate of 60 W, iNO reduced / by 3.8 ± 4.2 units (P = 0.002) and dyspnoea by 1.1 ± 1.2 Borg units (P < 0.001) in COPD, whereas no effect was observed in controls. Operating lung volumes and oxygen saturation were unaffected by iNO in both groups. iNO increased peak oxygen uptake in COPD, secondary to reduced / and dyspnoea. These data suggest that mild COPD patients demonstrate pulmonary microvascular dysfunction that contributes to increased / , dyspnoea and exercise intolerance. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD.
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http://dx.doi.org/10.1113/JP280913DOI Listing
March 2021

Elevated exercise ventilation in mild COPD is not linked to enhanced central chemosensitivity.

Respir Physiol Neurobiol 2021 02 5;284:103571. Epub 2020 Nov 5.

Respiratory Investigation Unit, Department of Medicine, Queen's University and Kingston Health Sciences Centre Kingston General Hospital Campus, Kingston, Ontario, Canada. Electronic address:

Background: The purpose of this study was to determine if altered central chemoreceptor characteristics contributed to the elevated ventilation relative to carbon dioxide production (V̇/V̇CO) 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 (V̇), the central chemoreflex ventilatory recruitment threshold for CO (VRTCO), and central chemoreflex sensitivity (V̇) were assessed using the modified Duffin's CO rebreathing method. Resting arterialized blood gas data were also obtained.

Results: At standardized exercise intensities, absolute V̇ and V̇/V̇CO were consistently elevated and the end-tidal partial pressure of CO was relatively decreased in mild COPD versus controls (all p < 0.05). There were no between-group differences in resting arterialized blood gas parameters, basal V̇, VRTCO, or V̇ (all p > 0.05).

Conclusion: These data have established that excessive exercise ventilation in mild COPD is not explained by altered central chemosensitivity.
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http://dx.doi.org/10.1016/j.resp.2020.103571DOI Listing
February 2021

Evaluation of Dynamic Respiratory Mechanical Abnormalities During Conventional CPET.

Front Med (Lausanne) 2020 10;7:548. Epub 2020 Sep 10.

Respiratory Investigation Unit, Division of Respirology, Department of Medicine, Kingston Health Sciences Centre & Queen's University, Kingston, ON, Canada.

Assessment of the ventilatory response to exercise is important in evaluating mechanisms of dyspnea and exercise intolerance in chronic cardiopulmonary diseases. The characteristic mechanical derangements that occur during exercise in chronic respiratory conditions have previously been determined in seminal studies using esophageal catheter pressure-derived measurements. In this brief review, we examine the emerging role and clinical utility of conventional assessment of dynamic respiratory mechanics during exercise testing. Thus, we provide a physiologic rationale for measuring operating lung volumes, breathing pattern, and flow-volume loops during exercise. We consider standardization of inspiratory capacity-derived measurements and their practical implementation in clinical laboratories. We examine the evidence that this iterative approach allows greater refinement in evaluation of ventilatory limitation during exercise than traditional assessments of breathing reserve. We appraise the available data on the reproducibility and responsiveness of this methodology. In particular, we review inspiratory capacity measurement and derived operating lung volumes during exercise. We demonstrate, using recent published data, how systematic evaluation of dynamic mechanical constraints, together with breathing pattern analysis, can provide valuable insights into the nature and extent of physiological impairment contributing to exercise intolerance in individuals with common chronic obstructive and restrictive respiratory disorders.
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http://dx.doi.org/10.3389/fmed.2020.00548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533639PMC
September 2020

Dyspnea and Exercise Limitation in Mild COPD: The Value of CPET.

Front Med (Lausanne) 2020 13;7:442. Epub 2020 Aug 13.

Respiratory Investigation Unit, Department of Medicine, Queen's University, Kingston, ON, Canada.

The majority of smokers with chronic obstructive pulmonary disease (COPD) have mild airflow limitation as determined by simple spirometry. Although small airway dysfunction is the hallmark of COPD, many studies attest to complex heterogeneous physiological impairments beyond increased airway resistance. These impairments are related to inflammation of lung parenchyma and its microvasculature, which is obscured by simple spirometry. Recent studies using advanced radiological imaging have highlighted significant structural abnormalities in smokers with relatively preserved spirometry. These important studies have generated considerable interest and have reinforced the pressing need to better understand the physiological consequences of various morphological abnormalities, and their impact on the clinical outcomes and natural history of COPD. The overarching objective of this review is to provide a concise overview of the importance and utility of cardiopulmonary exercise testing (CPET) in clinical and research settings. CPET uniquely allows evaluation of integrated abnormalities of the respiratory, cardio-circulatory, metabolic, peripheral muscle and neurosensory systems during increases in physiologic stress. This brief review examines the results of recent studies in mild COPD that have uncovered consistent derangements in pulmonary gas exchange and development of "restrictive" dynamic mechanics that together contribute to exercise intolerance. We examine the evidence that compensatory increases in inspiratory neural drive from respiratory control centers are required during exercise in mild COPD to maintain ventilation commensurate with increasing metabolic demand. The ultimate clinical consequences of this high inspiratory neural drive are earlier onset of critical respiratory mechanical constraints and increased perceived respiratory discomfort at relatively low exercise intensities.
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http://dx.doi.org/10.3389/fmed.2020.00442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438541PMC
August 2020

Inspiratory neural drive and dyspnea in interstitial lung disease: Effect of inhaled fentanyl.

Respir Physiol Neurobiol 2020 11 3;282:103511. Epub 2020 Aug 3.

Department of Medicine, Queen's University, Kingston Health Sciences Centre, Kingston, Ontario, Canada. Electronic address:

Background: Exertional dyspnea in interstitial lung disease (ILD) remains difficult to manage despite advances in disease-targeted therapies. Pulmonary opioid receptors present a potential therapeutic target for nebulized fentanyl to provide dyspnea relief.

Methods: ILD patients were characterized with reference to healthy volunteers. A randomized, double-blind, placebo-controlled crossover comparison of 100 mcg nebulized fentanyl vs placebo on dyspnea intensity and inspiratory neural drive (IND) during constant work rate (CWR) cycle exercise was performed in 21 ILD patients.

Results: Dyspnea intensity in ILD increased in association with an increase in IND (diaphragm activation) from a high resting value of 16.66 ± 6.52 %-60.04 ± 12.52 % of maximum (r = 0.798, p < 0.001). At isotime during CWR exercise, Borg dyspnea intensity ratings with fentanyl vs placebo were 4.1 ± 1.2 vs 3.8 ± 1.2, respectively (p = 0.174), and IND responses were also similar.

Conclusion: IND rose sharply during constant work rate exercise in association with dyspnea intensity in mild to moderate ILD but was not different after nebulized fentanyl compared with placebo.
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http://dx.doi.org/10.1016/j.resp.2020.103511DOI Listing
November 2020

Cardiac rehabilitation in the paediatric Fontan population: development of a home-based high-intensity interval training programme.

Cardiol Young 2020 Oct 27;30(10):1409-1416. Epub 2020 Jul 27.

Division of Pediatric Cardiology, Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada.

Introduction: We evaluated the safety and feasibility of high-intensity interval training via a novel telemedicine ergometer (MedBIKE™) in children with Fontan physiology.

Methods: The MedBIKE™ is a custom telemedicine ergometer, incorporating a video game platform and live feed of patient video/audio, electrocardiography, pulse oximetry, and power output, for remote medical supervision and modulation of work. There were three study phases: (I) exercise workload comparison between the MedBIKE™ and a standard cardiopulmonary exercise ergometer in 10 healthy adults. (II) In-hospital safety, feasibility, and user experience (via questionnaire) assessment of a MedBIKE™ high-intensity interval training protocol in children with Fontan physiology. (III) Eight-week home-based high-intensity interval trial programme in two participants with Fontan physiology.

Results: There was good agreement in oxygen consumption during graded exercise at matched work rates between the cardiopulmonary exercise ergometer and MedBIKE™ (1.1 ± 0.5 L/minute versus 1.1 ± 0.5 L/minute, p = 0.44). Ten youth with Fontan physiology (11.5 ± 1.8 years old) completed a MedBIKE™ high-intensity interval training session with no adverse events. The participants found the MedBIKE™ to be enjoyable and easy to navigate. In two participants, the 8-week home-based protocol was tolerated well with completion of 23/24 (96%) and 24/24 (100%) of sessions, respectively, and no adverse events across the 47 sessions in total.

Conclusion: The MedBIKE™ resulted in similar physiological responses as compared to a cardiopulmonary exercise test ergometer and the high-intensity interval training protocol was safe, feasible, and enjoyable in youth with Fontan physiology. A randomised-controlled trial of a home-based high-intensity interval training exercise intervention using the MedBIKE™ will next be undertaken.
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http://dx.doi.org/10.1017/S1047951120002097DOI Listing
October 2020

Measurement and Interpretation of Exercise Ventilatory Efficiency.

Front Physiol 2020 25;11:659. Epub 2020 Jun 25.

Clinical Physiology Laboratory, Division of Pulmonary Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada.

Cardiopulmonary exercise testing (CPET) is a method for evaluating pulmonary and cardiocirculatory abnormalities, dyspnea, and exercise tolerance in healthy individuals and patients with chronic conditions. During exercise, ventilation ( ) increases in proportion to metabolic demand [i.e., carbon dioxide production (CO)] to maintain arterial blood gas and acid-base balance. The response of relative to CO ( /CO) is commonly termed ventilatory efficiency and is becoming a common physiological tool, in conjunction with other key variables such as operating lung volumes, to evaluate exercise responses in patients with chronic conditions. A growing body of research has shown that the /CO response to exercise is elevated in conditions such as chronic heart failure (CHF), pulmonary hypertension (PH), interstitial lung disease (ILD), and chronic obstructive pulmonary disease (COPD). Importantly, this potentiated /CO response contributes to dyspnea and exercise intolerance. The clinical significance of ventilatory inefficiency is demonstrated by findings showing that the elevated /CO response to exercise is an independent predictor of mortality in patients with CHF, PH, and COPD. In this article, the underlying physiology, measurement, and interpretation of exercise ventilatory efficiency during CPET are reviewed. Additionally, exercise ventilatory efficiency in varying disease states is briefly discussed.
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http://dx.doi.org/10.3389/fphys.2020.00659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344219PMC
June 2020

Deterioration of Nighttime Respiratory Mechanics in COPD: Impact of Bronchodilator Therapy.

Chest 2021 01 27;159(1):116-127. Epub 2020 Jun 27.

Department of Medicine, Queen's University, Kingston, Canada; Division of Respiratory Medicine, Queen's University, Kingston, Canada. Electronic address:

Background: COPD is associated with nighttime respiratory symptoms, poor sleep quality, and increased risk of nocturnal death. Overnight deterioration of inspiratory capacity (IC) and FEV have been documented previously. However, the precise nature of this deterioration and mechanisms by which evening bronchodilation may mitigate this occurrence have not been studied.

Research Question: What is the effect of evening dosing of dual, long-acting bronchodilation on detailed nocturnal respiratory mechanics and inspiratory neural drive (IND)?

Study Design And Methods: 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.

Results: 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.

Interpretation: 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.
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http://dx.doi.org/10.1016/j.chest.2020.06.033DOI Listing
January 2021

The Effect of Carotid Chemoreceptor Inhibition on Exercise Tolerance in Chronic Heart Failure.

Front Physiol 2020 12;11:195. Epub 2020 Mar 12.

Division of Pulmonary Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Purpose: Chronic heart failure (CHF) is characterized by heightened sympathetic nervous activity, carotid chemoreceptor (CC) sensitivity, marked exercise intolerance and an exaggerated ventilatory response to exercise. The purpose of this study was to determine the effect of CC inhibition on exercise cardiovascular and ventilatory function, and exercise tolerance in health and CHF.

Methods: Twelve clinically stable, optimally treated patients with CHF (mean ejection fraction: 43 ± 2.5%) and 12 age- and sex-matched healthy controls were recruited. Participants completed two time-to-symptom-limitation (TLIM) constant load cycling exercise tests at 75% peak power output with either intravenous saline or low-dose dopamine (2 μg⋅kg⋅min; order randomized). Ventilation was measured using expired gas data and operating lung volume data were determined during exercise by inspiratory capacity maneuvers. Cardiac output was estimated using impedance cardiography, and vascular conductance was calculated as cardiac output/mean arterial pressure.

Results: There was no change in TLIM in either group with dopamine (CHF: saline 13.1 ± 2.4 vs. dopamine 13.5 ± 1.6 min, = 0.78; Control: saline 10.3 ± 1.2 vs. dopamine 11.5 ± 1.3 min, = 0.16). In CHF patients, dopamine increased cardiac output ( = 0.03), vascular conductance ( = 0.01) and oxygen delivery ( = 0.04) at TLIM, while ventilatory parameters were unaffected ( = 0.76). In controls, dopamine improved vascular conductance at TLIM ( = 0.03), but no other effects were observed.

Conclusion: Our findings suggest that the CC contributes to cardiovascular regulation during full-body exercise in patients with CHF, however, CC inhibition does not improve exercise tolerance.
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http://dx.doi.org/10.3389/fphys.2020.00195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080702PMC
March 2020

The supine position improves but does not normalize the blunted pulmonary capillary blood volume response to exercise in mild COPD.

J Appl Physiol (1985) 2020 04 12;128(4):925-933. Epub 2020 Mar 12.

Faculty of Medicine and Dentistry, Division of Pulmonary Medicine, University of Alberta, Edmonton, Alberta, Canada.

Patients with mild chronic obstructive pulmonary disease (COPD) demonstrate resting pulmonary vascular dysfunction as well as a blunted pulmonary diffusing capacity (DLCO) and pulmonary capillary blood volume (V) response to exercise. The transition from the upright to supine position increases central blood volume and perfusion pressure, which may overcome microvascular dysfunction in an otherwise intact alveolar-capillary interface. The present study examined whether the supine position normalized DLCO and V responses to exercise in mild COPD. Sixteen mild COPD participants and 13 age-, gender-, and height-matched controls completed DLCO maneuvers at rest and during exercise in the upright and supine position. The multiple -DLCO method was used to determine DLCO, V, and membrane diffusion capacity (D). All three variables were adjusted for alveolar volume (DLCOAdj, VAdj, and DAdj). The supine position reduced alveolar volume similarly in both groups, but oxygen consumption and cardiac output were unaffected. DLCOAdj, DAdj, and VAdj were all lower in COPD. These same variables all increased with upright and supine exercise in both groups. DLCOAdj was unaffected by the supine position. VAdj increased in the supine position similarly in both groups. DAdj was reduced in the supine position in both groups. While the supine position increased exercise VAdj in COPD, the increase was of similar magnitude to healthy controls; therefore, exercise V remained blunted in COPD. The persistent reduction in exercise DLCO and V when supine suggests that pulmonary vascular destruction is a contributing factor to the blunted DLCO and V response to exercise in mild COPD. Patients with mild chronic obstructive pulmonary disease demonstrate a combination of reversible pulmonary microvascular dysfunction and irreversible pulmonary microvascular destruction.
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http://dx.doi.org/10.1152/japplphysiol.00890.2019DOI Listing
April 2020

The effect of carotid chemoreceptor inhibition on exercise tolerance in chronic obstructive pulmonary disease: A randomized-controlled crossover trial.

Respir Med 2019 Nov - Dec;160:105815. Epub 2019 Nov 6.

Division of Pulmonary Medicine, Faculty of Medicine and Dentistry, University of Alberta, Canada; G.F. MacDonald Centre for Lung Health, Covenant Health, Edmonton, Alberta, Canada. Electronic address:

Background: Patients with chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory response to exercise, contributing to exertional dyspnea and exercise intolerance. We recently demonstrated enhanced activity and sensitivity of the carotid chemoreceptor (CC) in COPD which may alter ventilatory and cardiovascular regulation and negatively affect exercise tolerance. We sought to determine whether CC inhibition improves ventilatory and cardiovascular regulation, dyspnea and exercise tolerance in COPD.

Methods: Twelve mild-moderate COPD patients (FEV 83 ± 15 %predicted) and twelve age- and sex-matched healthy controls completed two time-to-symptom limitation (T) constant load exercise tests at 75% peak power output with either intravenous saline or low-dose dopamine (2 μg·kg·min, order randomized) to inhibit the CC. Ventilatory responses were evaluated using expired gas data and dyspnea was evaluated using a modified Borg scale. Inspiratory capacity maneuvers were performed to determine operating lung volumes. Cardiac output was estimated using impedance cardiography and vascular conductance was calculated as cardiac output/mean arterial pressure (MAP).

Results: At a standardized exercise time of 4-min and at T; ventilation, operating volumes and dyspnea were unaffected by dopamine in COPD patients and controls. In COPD, dopamine decreased MAP and increased vascular conductance at all time points. In controls, dopamine increased vascular conductance at T, while MAP was unaffected.

Conclusion: There was no change in time to exhaustion in either group with dopamine. These data suggest that the CC plays a role in cardiovascular regulation during exercise in COPD; however, ventilation, dyspnea and exercise tolerance were unaffected by CC inhibition in COPD patients.
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http://dx.doi.org/10.1016/j.rmed.2019.105815DOI Listing
August 2020

Ventilatory responses in males and females during graded exercise with and without thoracic load carriage.

Eur J Appl Physiol 2019 Feb 4;119(2):441-453. Epub 2018 Dec 4.

Faculty of Kinesiology, Sport, and Recreation, University of Alberta, 4-416D Van Vliet Complex, Edmonton, AB, T6G 2H9, Canada.

Purpose And Methods: To compare the effects of thoracic load carriage on the ventilatory and perceptual responses to graded exercise, 14 pairs of height-matched, physically active males and females completed randomly ordered modified Balke treadmill exercise tests with and without a correctly sized and fitted 20.4 kg backpack and work clothing. Subjects walked at 1.56 m.s while grade was increased by 2% every 2 min until exhaustion. Ventilatory responses were measured with open circuit spirometry and perceptual responses were evaluated using the modified Borg scale. Inspiratory capacity maneuvers were performed to calculate operating lung volumes.

Results: Despite height matching, males had significantly greater lung volumes and peak oxygen uptake ([Formula: see text]O). Peak [Formula: see text]O and ventilation ([Formula: see text]) were lower (p < 0.05) for all subjects under load. Throughout exercise, the ventilatory equivalents for [Formula: see text]O and carbon dioxide production were significantly higher in females, independent of condition. At similar relative submaximal intensities (%[Formula: see text]O), there was no difference in [Formula: see text] between conditions in either group, however, all subjects adopted a rapid and shallow breathing pattern under load with decreased tidal volume secondary to lower end-inspiratory lung volume. The relative changes in breathing pattern and operating lung volume between unloaded and loaded conditions were similar between males and females. Females reported significantly higher dyspnea ratings for a given [Formula: see text] compared to males; however, the relationship between dyspnea and [Formula: see text] was unaffected by load carriage.

Conclusion: The relative response patterns for ventilatory and perceptual responses to graded exercise with thoracic loading were similar in males and females.
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http://dx.doi.org/10.1007/s00421-018-4042-5DOI Listing
February 2019

Pulmonary capillary blood volume response to exercise is diminished in mild chronic obstructive pulmonary disease.

Respir Med 2018 12 19;145:57-65. Epub 2018 Oct 19.

Division of Pulmonary Medicine, Faculty of Medicine and Dentistry, University of Alberta, Canada; G.F. MacDonald Centre for Lung Health, Covenant Health, Edmonton, Alberta, Canada. Electronic address:

Background: Previous work suggests that mild chronic obstructive pulmonary disease (COPD) patients have greater lung dysfunction than previously appreciated from spirometry alone. There is evidence of pulmonary microvascular dysfunction in mild COPD, which may reduce diffusing capacity (DLCO) and increase ventilatory inefficiency during exercise. The purpose of this study was to determine if DLCO, pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) are diminished during exercise in mild COPD, and whether this is related to ventilatory inefficiency and dyspnea.

Methods: Seventeen mild COPD patients (FEV/FVC: 64 ± 4%, FEV = 94 ± 11%) and 17 age- and sex-matched controls were recruited. Ten moderate COPD patients were also tested for comparison (FEV = 66 ± 7%). DLCO, Vc, and Dm were determined using the multiple-fraction of inspired oxygen (FO) DLCO method at baseline and during steady-state cycle exercise at 40W, 50%, and 80% of V˙O. Using expired gas data, ventilatory inefficiency was assessed by V˙/V˙CO.

Results: Compared to controls, mild COPD had lower DLCO at baseline and during exercise secondary to diminished Vc (P < 0.05). No difference in Dm was observed between controls and mild COPD at rest or during exercise. Patients with high V˙/V˙CO (i.e. ≥34) had lower Vc and greater dyspnea ratings compared to control at 40W. Moderate COPD patients were unable to increase Vc with increasing exercise intensity, suggesting further pulmonary vascular impairment with increased obstruction severity.

Conclusion: Despite relatively minor airflow obstruction, mild COPD patients exhibit a diminished DLCO and capillary blood volume response to exercise, which appears to contribute to ventilatory inefficiency and greater dyspnea.
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http://dx.doi.org/10.1016/j.rmed.2018.10.015DOI Listing
December 2018

Exertional dyspnea and operating lung volumes in asthma.

J Appl Physiol (1985) 2018 09 7;125(3):870-877. Epub 2018 Jun 7.

Pulmonary Division, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, Alberta , Canada.

Dyspnea has been reported to be a main contributor to exercise avoidance in asthma. While traditional markers of ventilation do not explain the heightened dyspnea during exercise in patients with asthma, this study proposed that exertional dyspnea in asthma was due to high-operating lung volumes, which may be improved with a short-acting β2-agonist. On two separate days, 16 patients with asthma and 16 controls completed a lung function test and incremental exercise tests to exhaustion. On one of the days (order randomized), 400 µg salbutamol was administered before exercise. Inspiratory capacity (IC), inspiratory reserve volume (IRV), and dyspnea (modified Borg scale) were evaluated throughout exercise. Compared with controls, patients with asthma reported greater dyspnea at the same absolute submaximal workloads. Furthermore, patients with asthma demonstrated altered breathing responses to exercise, characterized by reduced IC and IRV throughout exercise compared with controls. The reduced IRV was associated with increased dyspnea in patients with asthma. Salbutamol did not affect dyspnea or operating lung volumes in either group. The increased perception of dyspnea during incremental exercise in patients with asthma appears to be secondary to a reduction in IRV, which is unaffected by an inhaled β2-agonist. NEW & NOTEWORTHY Increased exertional dyspnea in asthma appears to be due to high operating lung volumes and is not affected by salbutamol.
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http://dx.doi.org/10.1152/japplphysiol.00216.2018DOI Listing
September 2018

The carotid chemoreceptor contributes to the elevated arterial stiffness and vasoconstrictor outflow in chronic obstructive pulmonary disease.

J Physiol 2018 08 11;596(15):3233-3244. Epub 2018 Apr 11.

Division of Pulmonary Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

Key Points: The reason(s) for the increased central arterial stiffness in chronic obstructive pulmonary disease (COPD) are not well understood. In this study, we inhibited the carotid chemoreceptor with both low-dose dopamine and hyperoxia, and observed a decrease in central arterial stiffness and muscle sympathetic nervous activity in COPD patients, while no change was observed in age- and risk-matched controls. Carotid chemoreceptor inhibition increased vascular conductance, secondary to reduced arterial blood pressure in COPD patients. Findings from the current study suggest that elevated carotid chemoreceptor activity may contribute to the increased arterial stiffness typically observed in COPD patients.

Abstract: Chronic obstructive pulmonary disease (COPD) patients have increased central arterial stiffness and muscle sympathetic nervous activity (MSNA), both of which contribute to cardiovascular (CV) dysfunction and increased CV risk. Previous work suggests that COPD patients have elevated carotid chemoreceptor (CC) activity/sensitivity, which may contribute to the elevated MSNA and arterial stiffness. Accordingly, the effect of CC inhibition on central arterial stiffness, MSNA and CV function at rest in COPD patients was examined in a randomized placebo-controlled study. Thirteen mild-moderate COPD patients (forced expired volume in 1 s (FEV ) predicted ± SD: 83 ± 18%) and 13 age- and risk-matched controls completed resting CV function measurements with either i.v. saline or i.v. dopamine (2 μg kg  min ) while breathing normoxic or hyperoxic air (100% O ). On a separate day, a subset of COPD patients and controls completed MSNA measurements while breathing normoxic or hyperoxic air. Arterial stiffness was determined by pulse-wave velocity (PWV) and MSNA was measured by microneurography. Brachial blood flow was determined using Doppler ultrasound, cardiac output was estimated by impedance cardiography, and vascular conductance was calculated as flow/mean arterial pressure (MAP). CC inhibition with dopamine decreased central and peripheral PWV, and MAP (P < 0.05) while increasing vascular conductance in COPD. No change in CV function was observed with dopamine in controls. CC inhibition with hyperoxia decreased peripheral PWV and MSNA (P < 0.05) in COPD, while no change was observed in controls. CC inhibition decreased PWV and MSNA, and improved vascular conductance in COPD, suggesting that tonic CC activity is elevated at rest and contributes to the elevated arterial stiffness in COPD.
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http://dx.doi.org/10.1113/JP275762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068214PMC
August 2018

Influence of work clothing on physiological responses and performance during treadmill exercise and the Wildland Firefighter Pack Test.

Appl Ergon 2018 Apr 29;68:313-318. Epub 2017 Dec 29.

Faculty of Physical Education and Recreation, University of Alberta, Edmonton, AB, T6G 2H9, Canada.

This study investigated physiological responses and performance during three separate exercise challenges (Parts I, II, and III) with wildland firefighting work clothing ensemble (boots and coveralls) and a 20.4 kg backpack in four conditions: U-EX (no pack, exercise clothing); L-EX (pack, exercise clothing); U-W (no pack, work clothing); and, L-W (pack and work clothing). Part I consisted of randomly-ordered graded exercise tests, on separate days, in U-EX, L-EX and L-W conditions. Part II consisted of randomly-ordered bouts of sub-maximal treadmill exercise in the four conditions. In Part III, subjects completed, in random-order on separate days, 4.83 km Pack Tests in L-EX or L-W conditions. In Part I, peak oxygen uptake was reduced (p < .05) in L-W. In Part II, mass-specific oxygen uptake was significantly higher in both work clothing conditions. In Part III, Pack Test time was slower (p < .05) in L-W. These results demonstrate the negative impact of work clothing and load carriage on physiological responses to exercise and performance.
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http://dx.doi.org/10.1016/j.apergo.2017.12.010DOI Listing
April 2018

The Influence of Body Mass on Physical Fitness Test Performance in Male Firefighter Applicants.

J Occup Environ Med 2017 11;59(11):1101-1108

Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Alberta, T6G 2H9, Canada.

Objective: The influence of body mass on test performance was investigated in 414 male firefighter applicants who completed a maximal treadmill test and five task-simulation tests while dressed in fire protective ensemble.

Methods: Subjects were assigned to six mass categories from less than 70 kg to more than 110 kg, in 10 kg increments (n = 69 in each).

Results: Treadmill performance was lower (P < 0.05) in the two heaviest groups. Charged hose advance time was slower in the two lightest groups. The lightest group had slower times for weighted sled pull, forcible entry, and victim rescue tests. The heaviest group was slower on the ladder climb test.

Conclusion: Lighter subjects had a small advantage in endurance-oriented tests while higher mass appeared to improve performance slightly in strength-oriented tests. However, mass explained only 4% to 19% of the variance in performance.
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http://dx.doi.org/10.1097/JOM.0000000000001145DOI Listing
November 2017

The impact of thoracic load carriage up to 45 kg on the cardiopulmonary response to exercise.

Eur J Appl Physiol 2016 Sep 9;116(9):1725-34. Epub 2016 Jul 9.

Faculty of Physical Education and Recreation, University of Alberta, 4-427 Van Vliet Complex, Edmonton, AB, T6G 2H9, Canada.

Purpose: The purposes of this experiment were to, first, document the effect of 45-kg thoracic loading on peak exercise responses and, second, the effects of systematic increases in thoracic load on physiological responses to submaximal treadmill walking at a standardized speed and grade.

Methods: On separate days, 19 males (age 27 ± 5 years, height 180.0 ± 7.4 cm, mass 86.9 ± 15.1 kg) completed randomly ordered graded exercise tests to exhaustion in loaded (45 kg) and unloaded conditions. On a third day, each subject completed four randomly ordered, 10-min bouts of treadmill walking at 1.34 m s(-1) and 4 % grade in the following conditions: unloaded, and with backpacks weighted to 15, 30, and 45 kg.

Results: With 45-kg thoracic loading, absolute oxygen consumption ([Formula: see text]), minute ventilation, power output, and test duration were significantly decreased at peak exercise. End-inspiratory lung volume and tidal volume were significantly reduced with no changes in end-expiratory lung volume, breathing frequency, and the respiratory exchange ratio. Peak end-tidal carbon dioxide and the ratio of alveolar ventilation to carbon dioxide production were similar between conditions. The reductions in peak physiological responses were greater than expected based on previous research with lighter loads. During submaximal treadmill exercise, [Formula: see text] increased (P < 0.05) by 11.0 (unloaded to 15 kg), 14.5 (15-30 kg), and 18.0 % (30-45 kg) showing that the increase in exercise [Formula: see text] was not proportional to load mass.

Conclusion: These results provide further insight into the specificity of physiological responses to different types of load carriage.
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http://dx.doi.org/10.1007/s00421-016-3427-6DOI Listing
September 2016

Physiological and performance consequences of heavy thoracic load carriage in females.

Appl Physiol Nutr Metab 2016 Jul 8;41(7):741-8. Epub 2016 Mar 8.

a Faculty of Physical Education and Recreation, University of Alberta, Edmonton, AB T6G 2H9, Canada.

The purposes of this experiment were to study physiological responses to graded exercise to exhaustion (Part I) and ventilatory responses during 45 min of exercise (Part II) with and without a 25-kg backpack. In Part I, on separate days, 24 females completed randomly ordered modified Balke treadmill tests. Analysis revealed significant decreases in absolute peak oxygen uptake (3.5%), peak power output (20%), and test duration (40%) under load. There was a significant but modest negative relationship between body mass and the change in test duration between conditions (r = -0.44). While physiological responses to peak exercise were similar, exercise performance was negatively impacted under load. On separate days in Part II, 14 females completed randomly ordered, loaded and unloaded exercise challenges of submaximal treadmill walking at matched oxygen demands. Under load, breathing frequency, dead space, and minute ventilation were increased by 19.9%, 29.8%, and 11.6% (P < 0.05), respectively, while tidal volume and end-inspiratory lung volume decreased by 13.6% and 6.0% (P < 0.05), respectively. After loaded exercise, maximal inspiratory pressure was decreased by 11.5% (P < 0.05) with no changes in maximal expiratory pressure in either condition. Despite matched oxygen uptake between loaded and unloaded exercise challenges, perceived exertion and breathing discomfort were higher (P < 0.05) under load. With heavy load carriage, the altered breathing pattern led to increased dead space and minute ventilation, which likely contributed to higher perceptions of exercise stress and breathing discomfort. These results are similar to previous research in males and underscore the impact of heavy load carriage during exercise.
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http://dx.doi.org/10.1139/apnm-2016-0002DOI Listing
July 2016
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