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1. Pulmonary Function Laboratory and Respiratory Investigation Unit, Division of Respirology, Kingston Health Science Center & Queen’s University, Kingston, ON, Canada. 2. Unidade de Fisiologia Pulmonar, Hospital de Clínicas de Porto... more
1. Pulmonary Function Laboratory and Respiratory Investigation Unit, Division of Respirology, Kingston Health Science Center & Queen’s University, Kingston, ON, Canada. 2. Unidade de Fisiologia Pulmonar, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre (RS) Brasil. BACKGROUND Most patients with COPD show only mild airflow limitation on spirometry. Despite FEV1 normalcy, however, dyspnea on exertion is a frequent complaint. Structural and functional investigations in dyspneic patients with mild COPD showed important abnormalities in gas exchange efficiency, caused by a complex interaction among small airway disease, emphysema, and microvascular dysfunction.(1) Cardiopulmonary exercise testing is invariably useful to indicate whether patients presenting with out-of-proportion dyspnea can or cannot be ascribed to mild COPD.(2)
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Happy hypoxemia is an unspecified definition that is used in COVID-19 patients to define hypoxemia without dyspnoea. Dyspnoea is a very complex symptom, and although hypoxemia can cause breathlessness, dyspnoea is not related to... more
Happy hypoxemia is an unspecified definition that is used in COVID-19 patients to define hypoxemia without dyspnoea. Dyspnoea is a very complex symptom, and although hypoxemia can cause breathlessness, dyspnoea is not related to hypoxemia, but is more closely related to inspiratory drive and mechanical alterations. The lack of dyspnoea in the early stages of the disease is likely related to the absence of increased inspiratory drive due to compensatory mechanisms of hypoxemia, while in the advanced stages there is no evidence of a lack of dyspnoea in COVID-19 patients.
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The prevailing view is that exertional dyspnoea in patients with combined idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) can be largely explained by severe hypoxaemia. However, there is little evidence to support these... more
The prevailing view is that exertional dyspnoea in patients with combined idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) can be largely explained by severe hypoxaemia. However, there is little evidence to support these assumptions.We prospectively contrasted the sensory and physiological responses to exercise in 42 CPFE and 16 IPF patients matched by the severity of exertional hypoxaemia. Emphysema and pulmonary fibrosis were quantified using computed tomography. Inspiratory constraints were assessed in a constant work rate test: capillary blood gases were obtained in a subset of patients.CPFE patients had lower exercise capacity despite less extensive fibrosis compared to IPF (p=0.004 and 0.02, respectively). Exertional dyspnoea was the key limiting symptom in 24 CPFE patients who showed significantly lower transfer factor, arterial carbon dioxide tension and ventilatory efficiency (higher minute ventilation (V′E)/carbon dioxide output (V′CO2) ratio) compared to those wit...
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Research Interests: Medicine, Prospective studies, Humans, COPD, Internal Medicine, and 15 moreHealth Services, Female, Male, Dyspnea, Clinical Sciences, Aged, Middle Aged, Respiratory System, Chest, Disease Progression, Pulmonary disease, Proportional Hazards Models, Cohort Studies, Exacerbation, and Pittsburgh Sleep Quality Index
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Impaired aerobic function is a potential mechanism of exercise intolerance in patients with combined cardiorespiratory disease. We investigated the pathophysiological and sensory consequences of a low change in oxygen uptake... more
Impaired aerobic function is a potential mechanism of exercise intolerance in patients with combined cardiorespiratory disease. We investigated the pathophysiological and sensory consequences of a low change in oxygen uptake (ΔV′O2)/change in work rate (ΔWR) relationship during incremental exercise in patients with coexisting chronic obstructive pulmonary disease (COPD) and systolic heart failure (HF).After clinical stabilisation, 51 COPD–HF patients performed an incremental cardiopulmonary exercise test to symptom limitation. Cardiac output was non-invasively measured (impedance cardiography) in a subset of patients (n=18).27 patients presented with ΔV′O2/ΔWR below the lower limit of normal. Despite similar forced expiratory volume in 1 s and ejection fraction, the low ΔV′O2/ΔWR group showed higher end-diastolic volume, lower inspiratory capacity and lower transfer factor compared to their counterparts (p<0.05). Peak WR and peakV′O2were ∼15% and ∼30% lower, respectively, in the ...
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To determine whether upper airway mechanoreceptors partly subserve the ventilatory response to external mechanical loading in conscious humans, we studied 11 laryngectomized subjects. The oropharynx (OP) or tracheostomy was selectively... more
To determine whether upper airway mechanoreceptors partly subserve the ventilatory response to external mechanical loading in conscious humans, we studied 11 laryngectomized subjects. The oropharynx (OP) or tracheostomy was selectively loaded (in random order) by attaching the mouth or tracheal tube to a special pressure-generating apparatus, and steady-state ventilatory responses were recorded. Phasic negative pressure changes generated at the OP to simulate inspiratory resistive loading, expiratory resistive unloading, and elastic loading resulted in trivial prolongation of inspiratory duration by 12, 9, and 4%, respectively; other ventilatory variables were not significantly altered. Phasic positive pressure changes at the OP that simulated inspiratory resistive unloading and expiratory resistive loading had little effect on breathing pattern. When the above loads were applied via the tracheostomy, using pressures of similar magnitude, ventilatory responses were qualitatively sim...
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OBJECTIVE: To estimate the prevalence and determine the risk factors and health associations among individuals with combined chronic obstructive pulmonary disease and obesity.METHODS: Canadian national health survey data from 1994 to 2007... more
OBJECTIVE: To estimate the prevalence and determine the risk factors and health associations among individuals with combined chronic obstructive pulmonary disease and obesity.METHODS: Canadian national health survey data from 1994 to 2007 (n=650,000) were used. The presence of COPD was based on health professional-diagnosed self-report. The presence of obesity, defined by body mass index ≥30 kg/m2, was identified using self-reported and measured height and weight. Hospitalization, homecare use, physical activity assessments and socioeconomic data were all self-reported.RESULTS: In 2005, the prevalence of obesity in COPD (n=3470) and non-COPD (n=92,237) individuals was 24.6% and 17.1%, respectively (P<0.0001). In contrast to the non-COPD group, in which obesity prevalence increased by 38% over 14 years, obesity prevalence increased by only 5% in people with COPD over this same time period. Female sex was the only independent risk factor for obesity in COPD. Previous smoking, resid...
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Alpha-1 antitrypsin (A1AT) functions primarily to inhibit neutrophil elastase, and deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD). Severe A1AT deficiency occurs in one in 5000 to one... more
Alpha-1 antitrypsin (A1AT) functions primarily to inhibit neutrophil elastase, and deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD). Severe A1AT deficiency occurs in one in 5000 to one in 5500 of the North American population. While the exact prevalence of A1AT deficiency in patients with diagnosed COPD is not known, results from small studies provide estimates of 1% to 5%. The present document updates a previous Canadian Thoracic Society position statement from 2001, and was initiated because of lack of consensus and understanding of appropriate patients suitable for targeted testing for A1AT deficiency, and for the use of A1AT augmentation therapy. Using revised guideline development methodology, the present clinical practice guideline document systematically reviews the published literature and provides an evidence-based update. The evidence supports the practice that targeted testing for A1AT deficiency be considered in indivi...
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BACKGROUND: The lung function of patients with idiopathic pulmonary fibrosis (IPF) has not been characterized in detail.OBJECTIVE: To characterize the heterogeneous physiological abnormalities that exist in patients with IPF during their... more
BACKGROUND: The lung function of patients with idiopathic pulmonary fibrosis (IPF) has not been characterized in detail.OBJECTIVE: To characterize the heterogeneous physiological abnormalities that exist in patients with IPF during their initial clinical evaluation.METHODS: Lung function tests from 93 patients, performed within six months of the initial diagnosis of IPF, were obtained from a referral pulmonary function laboratory at a tertiary care hospital in Canada. A restrictive pattern was defined as total lung capacity (TLC) <95th percentile of predicted value. Patients with obstructive lung disease, lung cancer, emphysema and other restrictive lung diseases were excluded.RESULTS: On diagnosis, 73% of patients with IPF had a restrictive pattern, with a mean TLC of 72% of predicted. Mean forced vital capacity (FVC) was 71% and 44% of patients had an FVC <95th percentile. Mean diffusing capacity for carbon monoxide (DLco) was 60% and DLco/alveolar volume (VA) 92% of predict...
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Research Interests: Asthma, Medicine, Activities of Daily Living, Canada, Population, and 15 moreHumans, COPD, Female, Male, Clinical Sciences, Aged, Middle Aged, Adult, Bronchitis, Chronic obstructive pulmonary disease, Airway Obstruction, Cross Sectional Studies, Predictive value of tests, Acute Disease, and Exacerbation
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This study used a modified CO2 rebreathing procedure to examine the effect of gender on the chemoreflex control of breathing during wakefulness in healthy men ( n = 14) and women ( n = 14). Women were tested in the follicular phase of the... more
This study used a modified CO2 rebreathing procedure to examine the effect of gender on the chemoreflex control of breathing during wakefulness in healthy men ( n = 14) and women ( n = 14). Women were tested in the follicular phase of the menstrual cycle. During rebreathing trials, subjects hyperventilated to reduce the partial pressure of end-tidal CO2 (PetCO2) below 25 Torr and were then switched to a rebreathing bag containing a normocapnic hypoxic or hyperoxic gas mixture. During the trial, PetCO2 increased, while O2 was maintained at a constant level. The point at which ventilation began to rise as PetCO2 increased was identified as the ventilatory recruitment threshold (VRT). Ventilation below the VRT was measured, and the slope of the ventilatory response above the VRT was determined. Gender had no effect on the hyperoxic or hypoxic VRT for CO2. Central chemoreflex sensitivity was significantly greater in men than women but not after correction for forced vital capacity. Meas...
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To investigate energy metabolic and transporter characteristics in resting muscle of patients with moderate to severe chronic obstructive pulmonary disease [COPD; forced expiratory volume in 1 s (FEV1) = 42 ± 6.0% (mean ± SE)], tissue was... more
To investigate energy metabolic and transporter characteristics in resting muscle of patients with moderate to severe chronic obstructive pulmonary disease [COPD; forced expiratory volume in 1 s (FEV1) = 42 ± 6.0% (mean ± SE)], tissue was extracted from resting vastus lateralis (VL) of 9 COPD patients and compared with that of 12 healthy control subjects (FEV1= 114 ± 3.4%). Compared with controls, lower ( P < 0.05) concentrations (mmol/kg dry wt) of ATP (19.6 ± 0.65 vs. 17.8 ± 0.69) and phosphocreatine (81.3 ± 2.3 vs. 69.1 ± 4.2) were observed in COPD, which occurred in the absence of differences in the total adenine nucleotide and total creatine pools. Higher concentrations were observed in COPD for several glycolytic metabolites (glucose-1-phosphate, glucose-6-phosphate, fructose-6-phosphate, pyruvate) but not lactate. Glycogen storage was not affected by the disease (289 ± 20 vs. 269 ± 20 mmol glucosyl units/kg dry wt). Although no difference between groups was observed for th...
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Cardiopulmonary exercise testing is a noninvasive tool whose clinical value is not yet widely recognized. The technique involves breath-by-breath measurement of respiratory gas exchange during a symptom-limited exercise test, with... more
Cardiopulmonary exercise testing is a noninvasive tool whose clinical value is not yet widely recognized. The technique involves breath-by-breath measurement of respiratory gas exchange during a symptom-limited exercise test, with determination of maximal oxygen uptake and anaerobic threshold. These measurements serve as objective, reproducible indices of exercise capacity that can be applied to the management of various clinical problems. In addition, by permitting simultaneous assessment of circulatory and ventilatory reserves, the test can be especially helpful in the differential diagnosis of exertional dyspnea and fatigue. This paper reviews the physiology of gas exchange, the limitations of standard exercise tests, and the methodology and clinical applications of cardiopulmonary exercise testing.
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Research Interests: Algorithms, Sleep Medicine, Public Health, Medicine, Humans, and 15 moreObstructive sleep apnea, Clarity, Fluconazole, Patient Compliance, Phenotype, Executive Summary, Intensive Care Medicine, Multidisciplinary Approach, Medicine and Health Sciences, Beryllium, Leak, Cryptococcosis, Continuous Positive Airway Pressure, Medical and Health Sciences, and Apnea hypopnea index
Research Interests: Cardiology, Obesity, Medicine, Humans, COPD, and 15 moreInternal Medicine, Female, Male, Dyspnea, Lung, Aged, Middle Aged, Adult, Chronic obstructive pulmonary disease, Physical Exercise, Lung Volume Measurements, Cross Sectional Studies, Exercise Tolerance, Lung Volumes, and Medical and Health Sciences
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Educational aims To review current concepts of the mechanisms of symptom relief and improved exercise tolerance following pharmacological treatment in chronic obstructive pulmonary disease (COPD). To examine the relative responsiveness of... more
Educational aims To review current concepts of the mechanisms of symptom relief and improved exercise tolerance following pharmacological treatment in chronic obstructive pulmonary disease (COPD). To examine the relative responsiveness of new physiological outcome parameters in clinical trials. Summary Bronchodilator therapy is the first step in improving dyspnoea and exercise endurance in patients with COPD. Recent studies have challenged the long-held view that airway obstruction in COPD is irreversible. We now know that even in the setting of minor or no change in traditional spirometry, bronchodilator therapy is associated with consistent, and often impressive, reduction in lung hyperinflation. This pharmacological lung volume reduction is linked to improved inspiratory muscle function and enhanced neuro- mechanical coupling of the respiratory system during activity, even in those with advanced disease. Moreover, these improvements in dynamic mechanics provide a sound physiologi...
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The 3-min constant speed shuttle test (CSST) was used to examine the effect of tiotropium/olodaterol compared with tiotropium at reducing activity-related breathlessness in patients with chronic obstructive pulmonary disease (COPD).This... more
The 3-min constant speed shuttle test (CSST) was used to examine the effect of tiotropium/olodaterol compared with tiotropium at reducing activity-related breathlessness in patients with chronic obstructive pulmonary disease (COPD).This was a randomised, double-blind, two-period crossover study including COPD patients with moderate to severe pulmonary impairment, lung hyperinflation at rest and a Mahler Baseline Dyspnoea Index <8. Patients received 6 weeks of tiotropium/olodaterol 5/5 µg and tiotropium 5 µg in a randomised order with a 3-week washout period. The speed for the 3-min CSST was determined for each patient such that an intensity of breathing discomfort ≥4 (“somewhat severe”) on the modified Borg scale was reached at the end of a completed 3-min CSST.After 6 weeks, there was a decrease in the intensity of breathlessness (Borg dyspnoea score) at the end of the 3-min CSST from baseline with both tiotropium (mean –0.968, 95% CI −1.238– −0.698; n=100) and tiotropium/olodat...
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Background: The TORRACTO® study evaluated the effects of tiotropium/olodaterol versus placebo on endurance time during constant work-rate cycling and constant speed shuttle walking in patients with chronic obstructive pulmonary disease... more
Background: The TORRACTO® study evaluated the effects of tiotropium/olodaterol versus placebo on endurance time during constant work-rate cycling and constant speed shuttle walking in patients with chronic obstructive pulmonary disease (COPD) after 12 weeks of treatment. Methods: The effects of once-daily tiotropium/olodaterol (2.5/5 and 5/5 μg) on endurance time during constant work-rate cycle ergometry (CWRCE) after 6 and 12 weeks of treatment were compared with placebo in patients with COPD in a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Endurance time during the endurance shuttle walk test (ESWT) after 6 and 12 weeks of treatment was also evaluated in a subset of patients. Results: A total of 404 patients received treatment, with 165 participating in the ESWT substudy. A statistically significant improvement in endurance time during CWRCE was observed after 12 weeks (primary endpoint) with tiotropium/olodaterol 5/5 µg [14% ( p = 0.02)] but not w...
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Pulmonary rehabilitation (PR) participation is the standard of care for patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite bronchodilator therapies. However, there are questions about specific... more
Pulmonary rehabilitation (PR) participation is the standard of care for patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite bronchodilator therapies. However, there are questions about specific aspects of PR programming including optimal site of rehabilitation delivery, components of rehabilitation programming, duration of rehabilitation, target populations and timing of rehabilitation. The present document was compiled to specifically address these important clinical issues, using an evidence-based, systematic review process led by a representative interprofessional panel of experts. The evidence reveals there are no differences in major patient-related outcomes of PR between nonhospital- (community or home sites) or hospital-based sites. There is strong support to recommend that COPD patients initiate PR within one month following an acute exacerbation due to benefits of improved dyspnea, exercise tolerance and health-related quality of life r...
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Research Interests: Cardiology, Medicine, Humans, COPD, Internal Medicine, and 12 morePlacebo, Female, Male, Middle Aged, Chronic obstructive pulmonary disease, Cross-Over Studies, Exercise Tolerance, Severity of Illness Index, Inspiratory capacity, Tiotropium bromide, Bronchodilator agents, and Pulmonary Disease Chronic Obstructive
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We mimicked important mechanical and ventilatory aspects of restrictive lung disorders by employing chest wall strapping (CWS) and dead space loading (DS) in normal subjects to gain mechanistic insights into dyspnea causation and exercise... more
We mimicked important mechanical and ventilatory aspects of restrictive lung disorders by employing chest wall strapping (CWS) and dead space loading (DS) in normal subjects to gain mechanistic insights into dyspnea causation and exercise limitation. We hypothesized that thoracic restriction with increased ventilatory stimulation would evoke exertional dyspnea that was similar in nature to that experienced in such disorders. Twelve healthy young men [28 ± 2 (SE) yr of age] completed pulmonary function tests and maximal cycle exercise tests under four conditions, in randomized order: 1) control, 2) CWS to 60% of vital capacity, 3) added DS of 600 ml, and 4) CWS + DS. Measurements during exercise included cardiorespiratory parameters, esophageal pressure, and Borg scale ratings of dyspnea. Compared with control, CWS significantly reduced the tidal volume response to exercise, increased dyspnea intensity at any given work rate or ventilation, and thus limited exercise performance. DS s...
Research Interests: Perception, Medicine, Biological Sciences, Humans, Bicycling, and 15 moreSensation, Applied, Male, Exercise, Applied Physiology, Dyspnea, Respiration, Adult, Physical Exercise, Pulmonary ventilation, Cardiorespiratory Fitness, Constriction, Respiratory function tests, Medical and Health Sciences, and Dead Space
Research Interests: Cardiology, Exercise therapy, Medicine, Humans, COPD, and 15 moreInternal Medicine, Placebo, Female, Male, Dyspnea, Clinical Sciences, Middle Aged, Oxygen, Exercise Tolerance, Exercise Intolerance, Combined Modality Therapy, Respiratory function tests, Salbutamol, Bronchodilator agents, and Pulmonary Disease Chronic Obstructive
The prospect of digesting yet another set of ?best practice? guidelines is not an appealing one for the overwrought family physician. The Canadian Thoracic Society (CTS) panel, charged with the enormous task of developing new... more
The prospect of digesting yet another set of ?best practice? guidelines is not an appealing one for the overwrought family physician. The Canadian Thoracic Society (CTS) panel, charged with the enormous task of developing new evidencebased recommendations, was acutely aware of this. Nevertheless, they were convinced that the time was right to tackle this important educational initiative, and somehow managed to summon considerable reserves of energy and enthusiasm to produce an excellent, state-of-the-art compendium on the optimal management of this condition (1). Faced with the evidence that death rates from chronic obstructive pulmonary disease (COPD) continue to escalate in Canada and that its prevalence has risen to unprecedented levels (particularly in older women), the panel believed that there was an urgent need to raise awareness of this disease, and to optimize diagnosis and management (2).
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The case of a middle-aged, male smoker who presented with progressive severe dyspnea is described. The cause of the progressive severe dyspnea remained unexplained after a comprehensive history, physical examination, chest radiograph,... more
The case of a middle-aged, male smoker who presented with progressive severe dyspnea is described. The cause of the progressive severe dyspnea remained unexplained after a comprehensive history, physical examination, chest radiograph, electrocardiogram and spirometry. Subsequent investigations resulted in a diagnosis of localized pulmonary emphysema. Detailed exercise testing helped uncover the physiological basis of the patient’s extreme dyspnea.
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A case of chronic polyneuropathy that manifested with an unusual combination of vocal cord paralysis and respiratory muscle weakness is reported. In addition, results of an exercise test carried out to assess the severity and mechanisms... more
A case of chronic polyneuropathy that manifested with an unusual combination of vocal cord paralysis and respiratory muscle weakness is reported. In addition, results of an exercise test carried out to assess the severity and mechanisms of exertional breathlessness in this unique condition with combined obstructive and restrictive disorders are described.