Publications by authors named "Kathryn M Milne"

21 Publications

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Case Studies in Physiology: Cardiopulmonary exercise testing and inspiratory muscle training in a 59-year-old, 4 years after an extrapleural pneumonectomy.

J Appl Physiol (1985) 2021 Dec 28;131(6):1701-1707. Epub 2021 Oct 28.

Centre for Heart Lung Innovation, Providence Research, The University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia, Canada.

This case report characterizes the physiological responses to incremental cycling and determines the effects of 12 wk of inspiratory muscle training (IMT) on respiratory muscle strength, exercise capacity, and dyspnea in a physically active 59-yr-old female, 4 years after a left-sided extrapleural pneumonectomy (EPP). On separate days, a symptom-limited incremental exercise test and a constant work rate (CWR) test at 75% of peak work rate (WR) were completed, followed by 12 wk of IMT and another CWR test. IMT consisted of two sessions of 30 repetitions twice daily for 5 days per week. Physiological and perceptual variables were measured throughout each exercise test. The participant had a total lung capacity that was 43% predicted post-EPP. A rapid and shallow breathing pattern was adopted throughout exercise, and the ratio of minute ventilation to carbon dioxide output was elevated for a given work rate. Oxygen uptake was 71% predicted and WR was 88% predicted. Following IMT, maximal inspiratory pressure improved by 36% (-27.1 cmHO) and endurance time by 31 s, with no observable changes in any submaximal or peak cardiorespiratory variables during exercise. The intensity and unpleasantness of dyspnea increased by 2 and 3 Borg 0-10 units, respectively, at the highest equivalent submaximal exercise time achieved on both tests. Despite having undergone a significant reduction in lung volume post-EPP, the participant achieved a relatively normal peak incremental WR, which may reflect a high level of physical conditioning. This case report also demonstrates that IMT can effectively increase respiratory muscle strength several years following EPP. Constraints on tidal volume expansion and the adoption of a rapid and shallow breathing pattern result in a ventilatory limitation and increased ventilatory inefficiency during exercise in a patient several years after extrapleural pneumonectomy (EPP). Inspiratory muscle training can effectively increase respiratory muscle strength after EPP.
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http://dx.doi.org/10.1152/japplphysiol.00506.2021DOI Listing
December 2021

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

Med Sci Sports Exerc 2021 Dec;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

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

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

Pulmonary function and functional capacity in COVID-19 survivors with persistent dyspnoea.

Respir Physiol Neurobiol 2021 06 27;288:103644. Epub 2021 Feb 27.

Centre for Heart Lung Innovation, Providence Health Care Research Institute, The University of British Columbia and St. Paul's Hospital, 166-1081 Burrard Street, Vancouver, British Columbia, V6Z 1Y6, Canada; Department of Physical Therapy, The University of British Columbia, 2177 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada.

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), FEV (p = 0.04), D (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 D, 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.
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http://dx.doi.org/10.1016/j.resp.2021.103644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910142PMC
June 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

Mechanisms of orthopnoea in patients with advanced COPD.

Eur Respir J 2021 03 11;57(3). Epub 2021 Mar 11.

Division of Respiratory Medicine, Dept of Medicine, Queen's University and Kingston Health Sciences Centre, Kingston, ON, Canada

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 (EMG), oesophageal pressure ( ) and gastric pressure ( ), in both sitting and supine positions.Patients had severe airflow obstruction (forced expiratory volume in 1 s (FEV): 40±18% pred) and lung hyperinflation. Regardless of the position, patients had lower inspiratory capacity (IC) and higher IND for a given tidal volume ( ) ( greater neuromechanical dissociation (NMD)), higher intensity of breathing discomfort, higher minute ventilation (') and higher breathing frequency ( ) compared with controls (all p<0.05). For controls in a supine position, IC increased by 0.48 L sitting erect, with a small drop in ', mainly due to reduced (all p<0.05). By contrast, IC remained unaltered in patients with COPD, but dynamic lung compliance ( ) decreased (p<0.05) in the supine position. Breathing discomfort, inspiratory work of breathing (WOB), inspiratory effort, IND, NMD and neuroventilatory uncoupling all increased in COPD patients in the supine position (p<0.05), but not in the healthy controls. Orthopnoea was associated with acute changes in IND (r=0.65, p=0.01), neuroventilatory uncoupling (r=0.76, p=0.001) and NMD (r=0.73, p=0.002).In 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.
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http://dx.doi.org/10.1183/13993003.00754-2020DOI Listing
March 2021

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

Lung Function Testing in Chronic Obstructive Pulmonary Disease.

Clin Chest Med 2020 09;41(3):347-366

Division of Respiratory Medicine, Department of Medicine, Kingston Health Science Center, Queen's University, Richardson House, 102 Stuart Street, Kingston, Ontario K7L 2V6, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ccm.2020.06.004DOI Listing
September 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

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

Dyspnea in COPD: New Mechanistic Insights and Management Implications.

Adv Ther 2020 01 30;37(1):41-60. Epub 2019 Oct 30.

Division of Respirology, Department of Medicine, Kingston Health Sciences Centre and Queen's University, Kingston, ON, Canada.

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 (V), 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.
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http://dx.doi.org/10.1007/s12325-019-01128-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979461PMC
January 2020

Low resting diffusion capacity, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease.

J Appl Physiol (1985) 2019 10 1;127(4):1107-1116. Epub 2019 Aug 1.

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

The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (Dl) to dyspnea and exercise intolerance across the chronic obstructive pulmonary disease (COPD) continuum are poorly understood. COPD progression generally involves both Dl 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 (V̇o), Dl, and other resting physiological measures. Then, we stratified the sample into tertiles of forced expiratory volume in 1 s (FEV) and inspiratory capacity (IC) and compared dyspnea ratings, pulmonary gas exchange, and respiratory mechanics during exercise in groups with normal and low Dl [i.e.,
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http://dx.doi.org/10.1152/japplphysiol.00341.2019DOI Listing
October 2019

The Integrative Physiology of Exercise Training in Patients with COPD.

COPD 2019 04 16;16(2):182-195. Epub 2019 May 16.

a Respiratory Investigation Unit and Laboratory of Clinical Exercise Physiology, Division of Respirology, Department of Medicine, Kingston Health Science Center and Queen's University , Kingston , Ontario , Canada.

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.
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http://dx.doi.org/10.1080/15412555.2019.1606189DOI Listing
April 2019

Unraveling the Causes of Unexplained Dyspnea: The Value of Exercise Testing.

Clin Chest Med 2019 06;40(2):471-499

Department of Medicine, Queen's University, Kingston Health Sciences Centre, 102 Stuart Street, Kingston, Ontario K7L 2V6, Canada.

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.
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http://dx.doi.org/10.1016/j.ccm.2019.02.014DOI Listing
June 2019

The Pathophysiology of Dyspnea and Exercise Intolerance in Chronic Obstructive Pulmonary Disease.

Clin Chest Med 2019 06;40(2):343-366

Department of Medicine, Queen's University, Kingston Health Sciences Centre, 102 Stuart Street, Kingston, Ontario K7L 2V6, Canada.

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.
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http://dx.doi.org/10.1016/j.ccm.2019.02.007DOI Listing
June 2019

Systematic review of content and quality of idiopathic pulmonary fibrosis review articles.

ERJ Open Res 2018 Oct 21;4(4). Epub 2018 Dec 21.

Dept of Medicine, University of British Columbia, Vancouver, BC, Canada.

Narrative reviews are frequently accessed; however, the content and quality of review articles on idiopathic pulmonary fibrosis (IPF) have not been assessed. A systematic review assessed content and quality of narrative review articles that addressed the diagnosis or management of IPF and were published from 2001 to 2015. Article recommendations were assessed relative to contemporary IPF guidelines. Quality was assessed using the DISCERN instrument. Articles were predominantly written by physicians and published in respiratory journals. Conflicts of interest and sources of funding were reported in 52% and 24% of reviews, respectively. European authors were more likely to recommend bronchoscopy (adjusted p=0.02) and were more likely to recommend pirfenidone or nintedanib prior to publication of definitive clinical trials (adjusted p=0.04). A total of 39% of management-focused articles suggested therapies that were never recommended in guidelines. Predictors of higher article quality were citation of the contemporary IPF guideline (p=0.01) and more recent publication (p=0.001). Quality of reviews increased over time; however, review articles frequently made discordant recommendations compared to IPF guidelines. These findings indicate the need for authors, peer reviewers, editors and readers to critically appraise the content and quality of narrative reviews on IPF, and the need for frequent guideline updates to reflect new evidence.
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http://dx.doi.org/10.1183/23120541.00156-2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302207PMC
October 2018

Severity and features of frailty in systemic sclerosis-associated interstitial lung disease.

Respir Med 2017 08 25;129:1-7. Epub 2017 May 25.

Department of Medicine, University of British Columbia, Vancouver, Canada; Centre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada. Electronic address:

Background: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterized by multiple symptoms and comorbidities. The cumulative impact of these deficits can be summarized using the concept of frailty; however, frailty has not been characterized in patients with SSc-ILD.

Methods: Patients with SSc-ILD and non-CTD fibrotic ILD were recruited from specialized clinics. Frailty was assessed using a 42-item patient-reported Frailty Index, calculated as the proportion of reported deficits divided by the total number of surveyed items. Frailty was defined as a Frailty Index >0.21. Unadjusted and multivariate analyses were used to identify correlates of frailty.

Results: The study cohort included 86 patients with SSc-ILD and 167 patients with non-CTD fibrotic ILD. The mean age in SSc-ILD was 60.5 years, 80% were women, and on average patients had mild to moderate restrictive lung function impairment (mean FVC 78%-predicted, DLCO 51%-predicted). The mean Frailty Index was 0.23 ± 0.15, with 55% of the SSc-ILD population meeting criteria for frailty. Dyspnea had the strongest association with the Frailty Index (r = 0.62, p < 0.001) and was the only variable independently associated with frailty on multivariate analysis. Frailty severity was similar in SSc-ILD and non-CTD fibrotic ILD, including with adjustment for differences in baseline cohort characteristics.

Conclusion: Frailty is highly prevalent in patients with SSc-ILD, indicating that chronological age significantly underestimates biological age in this population. Dyspnea is the variable with the strongest association with frailty in SSc-ILD; however, future studies are needed to identify additional modifiable determinants of frailty and the ability of frailty to predict outcomes in SSc-ILD.
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http://dx.doi.org/10.1016/j.rmed.2017.05.012DOI Listing
August 2017

Frailty is common and strongly associated with dyspnoea severity in fibrotic interstitial lung disease.

Respirology 2017 05 9;22(4):728-734. Epub 2016 Nov 9.

Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Background And Objective: 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.

Methods: 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 score >0.21. 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.

Results: 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 (FEV ), diffusion capacity of the lung for carbon monoxide (DL ), ILD-gender, age and physiology (GAP) index, composite physiologic index and dyspnoea score. Dyspnoea severity was the strongest unadjusted predictor (r = 0.65, P < 0.001) and only independent predictor of the Frailty Index (0.034 increase in Frailty Index per 10-point increase in dyspnoea score; R  = 0.37; P < 0.001).

Conclusion: Frailty 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.
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http://dx.doi.org/10.1111/resp.12944DOI Listing
May 2017
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