21 results on '"James, Matthew D."'
Search Results
2. Compensatory responses to increased mechanical abnormalities in COPD during sleep
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Domnik, Nicolle J., Phillips, Devin B., James, Matthew D., Ayoo, Grace A., Taylor, Sarah M., Scheeren, Robin E., Di Luch, Amanda T., Milne, Kathryn M., Vincent, Sandra G., Elbehairy, Amany F., Crinion, Sophie J., Driver, Helen S., Neder, J. Alberto, and O’Donnell, Denis E.
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- 2022
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3. Elevated exercise ventilation in mild COPD is not linked to enhanced central chemosensitivity
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Phillips, Devin B, Domnik, Nicolle J, Elbehairy, Amany F, Preston, Megan E, Milne, Kathryn M, James, Matthew D, Vincent, Sandra G., Ibrahim-Masthan, Megha, Neder, J Alberto, and O’Donnell, Denis E
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- 2021
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4. Inspiratory neural drive and dyspnea in interstitial lung disease: Effect of inhaled fentanyl
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Milne, Kathryn M., Ibrahim-Masthan, Megha, Scheeren, Robin E., James, Matthew D., Phillips, Devin B., Moran-Mendoza, Onofre, JA, Neder, and O’Donnell, Denis E.
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- 2020
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5. Physiological Characterization of Preserved Ratio Impaired Spirometry in the CanCOLD Study: Implications for Exertional Dyspnea and Exercise Intolerance.
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Phillips, Devin B., James, Matthew D., Vincent, Sandra G., Elbehairy, Amany F., Neder, J. Alberto, Kirby, Miranda, Ora, Josuel, Day, Andrew G., Tan, Wan C., Bourbeau, Jean, and O'Donnell, Denis E.
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PULMONARY gas exchange ,CHRONIC obstructive pulmonary disease ,SPIROMETRY ,OBSTRUCTIVE lung diseases ,INTERMITTENT claudication ,DYSPNEA - Abstract
Rationale: It is increasingly recognized that adults with preserved ratio impaired spirometry (PRISm) are prone to increased morbidity. However, the underlying pathophysiological mechanisms are unknown. Objectives: Evaluate the mechanisms of increased dyspnea and reduced exercise capacity in PRISm. Methods: We completed a cross-sectional analysis of the CanCOLD (Canadian Cohort Obstructive Lung Disease) population-based study. We compared physiological responses in 59 participants meeting PRISm spirometric criteria (post-bronchodilator FEV
1 < 80% predicted and FEV1 /FVC ⩾ 0.7), 264 control participants, and 170 ever-smokers with chronic obstructive pulmonary disease (COPD), at rest and during cardiopulmonary exercise testing. Measurements and Main Results: Individuals with PRISm had lower total lung, vital, and inspiratory capacities than healthy controls (all P < 0.05) and minimal small airway, pulmonary gas exchange, and radiographic parenchymal lung abnormalities. Compared with healthy controls, individuals with PRISm had higher dyspnea/ V ˙ o2 ratio at peak exercise (4.0 ± 2.2 vs. 2.9 ± 1.9 Borg units/L/min; P < 0.001) and lower V ˙ o2peak (74 ± 22% predicted vs. 96 ± 25% predicted; P < 0.001). At standardized submaximal work rates, individuals with PRISm had greater Vt/inspiratory capacity (Vt%IC; P < 0.001), reflecting inspiratory mechanical constraint. In contrast to participants with PRISm, those with COPD had characteristic small airways dysfunction, dynamic hyperinflation, and pulmonary gas exchange abnormalities. Despite these physiological differences among the three groups, the relationship between increasing dyspnea and Vt%IC during cardiopulmonary exercise testing was similar. Resting IC significantly correlated with V ˙ o2peak (r = 0.65; P < 0.001) in the entire sample, even after adjusting for airflow limitation, gas trapping, and diffusing capacity. Conclusions: In individuals with PRISm, lower exercise capacity and higher exertional dyspnea than healthy controls were mainly explained by lower resting lung volumes and earlier onset of dynamic inspiratory mechanical constraints at relatively low work rates. Clinical trial registered with (NCT00920348). [ABSTRACT FROM AUTHOR]- Published
- 2024
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6. Systemic Determinants of Exercise Intolerance in Patients With Fibrotic Interstitial Lung Disease and Severely Impaired DLCO.
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Smyth, Reginald M., James, Matthew D., Vincent, Sandra G., Milne, Kathryn M., Marillier, Mathieu, Domnik, Nicolle J., Parker, Christopher M., de-Torres, Juan P., Moran-Mendoza, Onofre, Phillips, Devin B., O'Donnell, Denis E., and Neder, J. Alberto
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EXERCISE tests ,LUNG volume measurements ,STATISTICS ,IDIOPATHIC pulmonary fibrosis ,EXERCISE tolerance ,CARBON monoxide ,ANALYSIS of variance ,CARDIOPULMONARY system ,LUNGS ,CROSS-sectional method ,ONE-way analysis of variance ,INTERSTITIAL lung diseases ,OXYGEN saturation ,RESPIRATORY measurements ,CASE-control method ,DYSPNEA ,PULMONARY function tests ,EXERCISE intensity ,DESCRIPTIVE statistics ,CHI-squared test ,SPIROMETRY ,EXPIRATORY flow ,DATA analysis ,PULMONARY gas exchange ,ANAEROBIC threshold ,DISEASE complications - Abstract
Background: The precise mechanisms driving poor exercise tolerance in patients with fibrotic interstitial lung diseases (fibrotic ILDs) showing a severe impairment in single-breath lung diffusing capacity for carbon monoxide (D
LCO < 40% predicted) are not fully understood. Rather than only reflecting impaired O2 transfer, a severely impaired DLCO may signal deranged integrative physiologic adjustments to exercise that jointly increase the burden of exertional symptoms in fibrotic ILD. Methods: Sixty-seven subjects (46 with idiopathic pulmonary fibrosis, 24 showing DLCO < 40%) and 22 controls underwent pulmonary function tests and an incremental cardiopulmonary exercise test with serial measurements of operating lung volumes and 0-10 Borg dyspnea and leg discomfort scores. Results: Subjects from the DLCO < 40% group showed lower spirometric values, more severe restriction, and lower alveolar volume and transfer coefficient compared to controls and participants with less impaired DLCO (P < .05). Peak work rate was -45% (vs controls) and -20% (vs DLCO > 40%) lower in the former group, being associated with lower (and flatter) O2 pulse, an earlier lactate (anaerobic) threshold, heightened submaximal ventilation, and lower SpO2 . Moreover, critically high inspiratory constrains were reached at lower exercise intensities in the DLCO < 40% group (P < .05). In association with the greatest leg discomfort scores, they reported the highest dyspnea scores at a given work rate. Between-group differences lessened or disappeared when dyspnea intensity was related to indexes of increased demand-capacity imbalance, that is, decreasing submaximal, dynamic ventilatory reserve, and inspiratory reserve volume/total lung capacity (P > .05). Conclusions: A severely reduced DLCO in fibrotic ILD signals multiple interconnected derangements (cardiovascular impairment, an early shift to anaerobic metabolism, excess ventilation, inspiratory constraints, and hypoxemia) that ultimately lead to limiting respiratory (dyspnea) and peripheral (leg discomfort) symptoms. DLCO < 40%, therefore, might help in clinical decision-making to indicate the patient with fibrotic ILD who might derive particular benefit from pharmacologic and non-pharmacologic interventions aimed at lessening these systemic abnormalities. [ABSTRACT FROM AUTHOR]- Published
- 2023
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7. Dynamic Ventilatory Reserve During Incremental Exercise: Reference Values and Clinical Validation in Chronic Obstructive Pulmonary Disease.
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Berton, Danilo C., Plachi, Franciele, James, Matthew D., Vincent, Sandra G., Smyth, Reginald M., Domnik, Nicolle J., Phillips, Devin B., de-Torres, Juan P., Nery, Luiz E., O'Donnell, Denis E., and Neder, J. Alberto
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EXERCISE tolerance ,VENTILATION ,CHRONIC obstructive pulmonary disease ,REFERENCE values ,OBSTRUCTIVE lung diseases ,EXERCISE tests - Abstract
Rationale: Ventilatory demand-capacity imbalance, as inferred based on a low ventilatory reserve, is currently assessed only at peak cardiopulmonary exercise testing (CPET). Peak ventilatory reserve, however, is poorly sensitive to the submaximal, dynamic mechanical ventilatory abnormalities that are key to dyspnea genesis and exercise intolerance. Objectives: After establishing sex- and age-corrected norms for dynamic ventilatory reserve at progressively higher work rates, we compared peak and dynamic ventilatory reserve for their ability to expose increased exertional dyspnea and poor exercise tolerance in mild to very severe chronic obstructive pulmonary disease (COPD). Methods: We analyzed resting functional and incremental CPET data from 275 controls (130 men, aged 19-85 yr) and 359 Global Initiative for Chronic Obstructive Lung Disease patients with stage 1-4 obstruction (203 men) who were prospectively recruited for previous ethically approved studies in three research centers. In addition to peak and dynamic ventilatory reserve (12[ventilation / estimated maximal voluntary ventilation]3100), operating lung volumes and dyspnea scores (0-10 on the Borg scale) were obtained. Results: Dynamic ventilatory reserve was asymmetrically distributed in controls; thus, we calculated its centile distribution at every 20 W. The lower limit of normal (lower than the fifth centile) was consistently lower in women and older subjects. Peak and dynamic ventilatory reserve disagreed significantly in indicating an abnormally low test result in patients: whereas approximately 50% of those with a normal peak ventilatory reserve showed a reduced dynamic ventilatory reserve, the opposite was found in approximately 15% (P,0.001). Irrespective of peak ventilatory reserve and COPD severity, patients who had a dynamic ventilatory reserve below the lower limit of normal at an isowork rate of 40W had greater ventilatory requirements, prompting earlier attainment of critically low inspiratory reserve. Consequently, they reported higher dyspnea scores, showing poorer exercise tolerance compared with those with preserved dynamic ventilatory reserve. Conversely, patients with preserved dynamic ventilatory reserve but reduced peak ventilatory reserve reported the lowest dyspnea scores, showing the best exercise tolerance. Conclusions: Reduced submaximal dynamic ventilatory reserve, even in the setting of preserved peak ventilatory reserve, is a powerful predictor of exertional dyspnea and exercise intolerance in COPD. This new parameter of ventilatory demand-capacity mismatch may enhance the yield of clinical CPET in the investigation of activity-related breathlessness in individual patients with COPD and other prevalent cardiopulmonary diseases. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Neurophysiological mechanisms of exertional dyspnea in post-pulmonary embolism syndrome.
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Milne, Kathryn M., James, Matthew D., Smyth, Reginald M., Vincent, Sandra G., Singh, Namisha, D'Arsigny, Christine L., de-Torres, Juan P., de Wit, Kerstin, Johri, Amer, Neder, J. Alberto, O'Donnell, Denis E., and Phillips, Devin B.
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Following pulmonary embolism (PE), a third of patients develop persistent dyspnea, which is commonly termed the post-PE syndrome. The neurophysiological underpinnings of exertional dyspnea in patients with post-PE syndrome without pulmonary hypertension (PH) are unclear. Thus, the current study determined if abnormally high inspiratory neural drive (IND) due, in part, to residual pulmonary gas-exchange abnormalities, was linked to heightened exertional dyspnea and exercise limitation, in such patients. Fourteen participants with post-PE syndrome (without resting PH) and 14 age-, sex-, and body mass index-matched healthy controls undertook pulmonary function testing and a symptom-limited cycle cardiopulmonary exercise test with measurements of IND (diaphragmatic electromyography), ventilatory requirements for CO
2 (VE/VCO2 ), and perceived dyspnea intensity (modified Borg 0-10 scale). Post-PE (vs. control) had a reduced resting transfer coefficient for carbon monoxide (KCO : 84 ± 15 vs. 104 ± 14%pred, P < 0.001) and peak oxygen uptake (VO2peak) (76 ± 14 vs. 124 ± 28%pred, P < 0.001). IND and VE/VCO2 were higher in post-PE than controls at standardized submaximal work rates (P < 0.05). Dyspnea increased similarly in both groups as a function of increasing IND but was higher in post-PE at standardized submaximal work rates (P < 0.05). High IND was associated with low KCO (r = -0.484, P < 0.001), high VE/VCO2 nadir (r = 0.453, P < 0.001), and low VO2peak (r = -0.523, P < 0.001). In patients with post-PE syndrome, exercise IND was higher than controls and was associated with greater dyspnea intensity. The heightened IND and dyspnea in post-PE, in turn, were strongly associated with low resting KCO and high exercise VE/VCO2 , which suggest important pulmonary gas-exchange abnormalities in this patient population. NEW & NOTEWORTHY This study is the first to show that increased exertional dyspnea in patients with post-pulmonary embolism (PE) syndrome, without overt pulmonary hypertension, was strongly associated with elevated inspiratory neural drive (IND) to the diaphragm during exercise, compared with healthy controls. The greater IND was associated with impairments in pulmonary gas exchange and significant deconditioning. Our results help to explain why many patients with post-PE syndrome report significant dyspnea at relatively low levels of physical activity. [ABSTRACT FROM AUTHOR]- Published
- 2023
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9. Pulmonary Vascular Volume by Quantitative CT in Dyspneic Smokers with Minor Emphysema.
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Elbehairy, Amany F., Vincent, Sandra G., Phillips, Devin B., James, Matthew D., Veugen, Jenna, Parraga, Grace, O’Donnell, Denis E., and Neder, J. Alberto
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Reduced lung diffusing capacity for carbon monoxide (DL
CO ) at rest and increased ventilation (⩒E )-carbon dioxide output (⩒CO2 ) during exercise are frequent findings in dyspneic smokers with largely preserved FEV1 . It remains unclear whether low DLCO and high ⩒E -⩒CO2 are mere reflections of alveolar destruction (i.e. emphysema) or impaired pulmonary perfusion in non-emphysematous tissue contributes to these functional abnormalities. Sixty-four smokers (41 males, FEV1 = 84 ± 13%predicted) underwent pulmonary function tests, an incremental exercise test, and quantitative chest computed tomography. Total pulmonary vascular volume (TPVV) was calculated for the entire segmented vascular tree (VIDA Vision™). Using the median % low attenuation area (-950 HU), participants were dichotomized into “Trace” or “Mild” emphysema (E), each group classified into preserved versus reduced DLCO . Within each emphysema subgroup, participants with abnormally low DLCO showed lower TPVV, higher ⩒E -⩒CO2 , and exertional dyspnea than those with preserved DLCO (p < 0.05). TPVV (r = 0.34; p = 0.01), but not emphysema (r = −0.05; p = 0.67), correlated with lower DLCO after adjusting for age and height. Despite lower emphysema burden, Trace-E participants with reduced DLCO had lower TPVV, higher dyspnea, and lower peak work rate than the Mild-E with preserved DLCO (p < 0.05). Interestingly, TPVV (but not emphysema) correlated inversely with both dyspnea-work rate (r = −0.36, p = 0.004) and dyspnea-⩒E slopes (r = −0.40, p = 0.001). Reduced pulmonary vascular volume adjusted by emphysema extent is associated with low DLCO and heightened exertional ventilation in dyspneic smokers with minor emphysema. Impaired perfusion of non-emphysematous regions of the lungs has greater functional and clinical consequences than hitherto assumed in these subjects. [ABSTRACT FROM AUTHOR]- Published
- 2023
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10. Exertional dyspnoea in patients with mild‐to‐severe chronic obstructive pulmonary disease: neuromechanical mechanisms.
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James, Matthew D., Phillips, Devin B., Vincent, Sandra G., Abdallah, Sara J., Donovan, Adamo A., de‐Torres, Juan P., Neder, J. Alberto, Smith, Benjamin M., Jensen, Dennis, and O'Donnell, Denis E.
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CHRONIC obstructive pulmonary disease , *PULMONARY gas exchange , *DYSPNEA , *EXERCISE tests , *ORTHOSTATIC intolerance - Abstract
In patients with chronic obstructive pulmonary disease (COPD), exertional dyspnoea generally arises when there is imbalance between ventilatory demand and capacity, but the neurophysiological mechanisms are unclear. We therefore determined if disparity between elevated inspiratory neural drive (IND) and tidal volume (VT) responses (neuromechanical dissociation) impacted dyspnoea intensity and quality during exercise, across the COPD severity spectrum. In this two‐centre, cross‐sectional observational study, 89 participants with COPD divided into tertiles of FEV1 %predicted (Tertile 1 = FEV1 = 87 ± 9%, Tertile 2 = 60 ± 9%, Tertile 3 = 32 ± 8%) and 18 non‐smoking controls, completed a symptom‐limited cardiopulmonary exercise test (CPET) with measurement of IND by diaphragm electromyography (EMGdi (%max)). The association between increasing dyspnoea intensity and EMGdi (%max) during CPET was strong (r = 0.730, P < 0.001) and not different between the four groups who showed marked heterogeneity in pulmonary gas exchange and mechanical abnormalities. Significant inspiratory constraints (tidal volume/inspiratory capacity (VT/IC) ≥ 70%) and onset of neuromechanical dissociation (EMGdi (%max):VT/IC > 0.75) occurred at progressively lower minute ventilation (V̇E${\dot{V}}_{{\rm{E}}}$) from Control to Tertile 3. Lower resting IC meant earlier onset of neuromechanical dissociation, heightened dyspnoea intensity and greater propensity (93% in Tertile 3) to select qualitative descriptors of 'unsatisfied inspiration'. We concluded that, regardless of marked variation in mechanical and pulmonary gas exchange abnormalities in our study sample, exertional dyspnoea intensity was linked to the magnitude of EMGdi (%max). Moreover, onset of critical inspiratory constraints and attendant neuromechanical dissociation amplified dyspnoea intensity at higher exercise intensities. Simple measurements of IC and breathing pattern during CPET provide useful insights into mechanisms of dyspnoea and exercise intolerance in individuals with COPD. Key points: Dyspnoea during exercise is a common and troublesome symptom reported by patients with chronic obstructive pulmonary disease (COPD) and is linked to an elevated inspiratory neural drive (IND). The precise mechanisms of elevated IND and dyspnoea across the continuum of airflow obstruction severity in COPD remains unclear.The present study sought to determine the mechanisms of elevated IND (by diaphragm EMG, EMGdi (%max)) and dyspnoea during cardiopulmonary exercise testing (CPET) across the continuum of COPD severity.There was a strong association between increasing dyspnoea intensity and EMGdi (%max) during CPET across the COPD continuum despite significant heterogeneity in underlying pulmonary gas exchange and respiratory mechanical impairments.Critical inspiratory constraints occurred at progressively lower ventilation during exercise with worsening severity of COPD. This was associated with the progressively lower resting inspiratory capacity with worsening disease severity.Earlier critical inspiratory constraint was associated with earlier neuromechanical dissociation and greater likelihood of reporting the sensation of 'unsatisfied inspiration'. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Physiological predictors of morbidity and mortality in COPD: the relative importance of reduced inspiratory capacity and inspiratory muscle strength.
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Phillips, Devin B., James, Matthew D., O'Donnell, Conor D., Vincent, Sandra G., Webb, Katherine A., de-Torres, Juan P., Neder, J. Alberto, and O'Donnell, Denis E.
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RESPIRATORY muscles ,MUSCLE strength ,CHRONIC obstructive pulmonary disease ,EXERCISE tests ,PULMONARY function tests ,RESPIRATORY obstructions - Abstract
Low resting inspiratory capacity (IC) and low maximal inspiratory pressure (MIP) have previously been linked to exertional dyspnea, exercise limitation, and poor survival in chronic obstructive pulmonary disease (COPD). The interaction and relative contributions of these two related variables to important clinical outcomes are unknown. The objective of the current study was to examine the interaction between resting IC and MIP (both % predicted), exertional dyspnea, exercise capacity, and long-term survival in patients with COPD. Two hundred and eighty-five patients with mild to advanced COPD completed standard lung function testing and a cycle cardiopulmonary exercise test. Multiple regression determined predictors of the exertional dyspnea-ventilation slope and peak oxygen uptake (...O
2peak ). Cox regression determined predictors of 10-year mortality. IC was associated with the dyspnea-ventilation slope (standardized β = -0.42, P < 0.001), whereas MIP was excluded from the regression model (P = 0.918). IC and MIP were included in the final model to predict VO2peak. However, the standardized β was greater for IC (0.43) than MIP (0.22). After adjusting for age, sex, body mass index, cardiovascular risk, airflow obstruction, and diffusing capacity, resting IC was independently associated with 10-year all-cause mortality (hazard ratio = 1.25, confidence interval5%_95% = 1.16-1.34, P < 0.001), whereas MIP was excluded from the final model (all P = 0.829). Low resting IC was consistently linked to heightened dyspnea intensity, low ...O2peak , and worse survival in COPD even after accounting for airway obstruction, inspiratory muscle strength, and diffusing capacity. These results support the use of resting IC as an important physiological biomarker closely linked to key clinical outcomes in COPD. NEW & NOTEWORTHY To our knowledge, this study is the first to show an independent association between low resting inspiratory capacity (IC) and, severe exertional dyspnea, exercise limitation, and increased mortality risk, after accounting for the severity of airway obstruction, inspiratory muscle strength, and diffusing capacity. These results support the use of resting IC as an important independent physiological biomarker closely linked to key clinical outcomes in COPD. [ABSTRACT FROM AUTHOR]- Published
- 2022
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12. Impaired Ventilatory Efficiency, Dyspnea, and Exercise Intolerance in Chronic Obstructive Pulmonary Disease: Results from the CanCOLD Study.
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Phillips, Devin B., Elbehairy, Amany F., James, Matthew D., Vincent, Sandra G., Milne, Kathryn M., de-Torres, Juan P., Neder, J. Alberto, Kirby, Miranda, Jensen, Dennis, Stickland, Michael K., Guenette, Jordan A., Smith, Benjamin M., Aaron, Shawn D., Tan, Wan C., Bourbeau, Jean, O'Donnel, Denis E., O'Donnell, Denis E, and CanCOLD Collaborative Research Group and the Canadian Respiratory Research Network
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EXERCISE tests ,EXERCISE tolerance ,DYSPNEA ,OBSTRUCTIVE lung diseases ,CARBON dioxide ,RESEARCH funding ,PULMONARY gas exchange ,DISEASE complications - Abstract
Rationale: Impaired exercise ventilatory efficiency (high ventilatory requirements for CO2 [[Formula: see text]e/[Formula: see text]co2]) provides an indication of pulmonary gas exchange abnormalities in chronic obstructive pulmonary disease (COPD). Objectives: To determine 1) the association between high [Formula: see text]e/[Formula: see text]co2 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. Impaired exercise ventilatory efficiency was defined by a nadir [Formula: see text]e/[Formula: see text]co2 above the upper limit of normal (ULN), using population-based normative values. Measurements and Main Results: Participants included 445 never-smokers, 381 ever-smokers without airflow obstruction, 224 with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 COPD, and 200 with GOLD 2-4 COPD. Participants with [Formula: see text]e/[Formula: see text]co2 above the ULN were more likely to have activity-related dyspnea (Medical Research Council dyspnea scale ⩾ 2; odds ratio [5-95% confidence intervals], 1.77 [1.31 to 2.39]) and abnormally low peak [Formula: see text]o2 ([Formula: see text]o2peak below the lower limit of normal; odds ratio, 4.58 [3.06 to 6.86]). The Kco had a stronger correlation with nadir [Formula: see text]e/[Formula: see text]co2 (r = -0.38; P < 0.001) than other relevant lung function and computed tomography metrics. The prevalence of [Formula: see text]e/[Formula: see text]co2 above the ULN was 24% in COPD (similar in GOLD 1 and 2 through 4), which was greater than in never-smokers (13%) and ever-smokers (12%). Conclusions: [Formula: see text]e/[Formula: see text]co2 above the ULN was associated with greater dyspnea and low [Formula: see text]o2peak 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. [ABSTRACT FROM AUTHOR]
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- 2022
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13. Electronic detection of single-base mismatches in DNA with ferrocene-modified probes
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C.J. Yu, Yanjian Wan, Yowanto, Handy, Jie Li, Chunlin Tao, James, Matthew D., Blackburn, Gary F., Meade, Thomas J., and Tan, Christine L.
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DNA probes -- Research ,Mutation (Biology) -- Analysis ,Mutation (Biology) -- Identification and classification ,Chemistry - Abstract
The detection of a point mutation using dual-signaling probes on CMS-DNA arrays coupled to an electrochemical reader is described. The results show that rapid and accurate detection of a single-base mismatch is achieved by using these dual-signaling probes on CMS-DNA chips.
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- 2001
14. Mechanisms of Exertional Dyspnea in Patients with Mild COPD and a Low Resting DLCO.
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James, Matthew D., Phillips, Devin B., Elbehairy, Amany F., Milne, Kathryn M., Vincent, Sandra G., Domnik, Nicolle J., de Torres, Juan P., Neder, J. Alberto, and O'Donnell, Denis E.
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OBSTRUCTIVE lung diseases , *DYSPNEA , *RESPIRATORY mechanics , *LUNG volume , *LUNG volume measurements - Abstract
Patients with mild chronic obstructive pulmonary disease (COPD) and lower resting diffusing capacity for carbon monoxide (DLCO) often report troublesome dyspnea during exercise although the 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 (n = 15) and without (n = 13) DLCO less than the lower limit of normal (
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- 2021
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15. Mechanisms of Exertional Dyspnea in Patients with Mild COPD and a Low Resting DLCO.
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James, Matthew D., Phillips, Devin B., Elbehairy, Amany F., Milne, Kathryn M., Vincent, Sandra G., Domnik, Nicolle J., de Torres, Juan P., Neder, J. Alberto, and O'Donnell, Denis E.
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OBSTRUCTIVE lung diseases ,DYSPNEA ,RESPIRATORY mechanics ,LUNG volume ,LUNG volume measurements - Abstract
Patients with mild chronic obstructive pulmonary disease (COPD) and lower resting diffusing capacity for carbon monoxide (DL
CO ) 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 (n = 15) and without (n = 13) DLCO less than the lower limit of normal (2 (V̇ E /V̇CO2 ), and respiratory mechanics during incremental cycle exercise in the three groups. Spirometry and resting lung volumes were similar between COPD groups. During exercise, dyspnea, IND and V̇E /V̇CO2 were higher at equivalent work rates (WR) in the DLCO CO CO CO E/V̇CO 2 at a given work rate. Higher ventilatory requirements in the DLCO - Published
- 2021
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16. Reduced exercise tolerance in mild chronic obstructive pulmonary disease: The contribution of combined abnormalities of diffusing capacity for carbon monoxide and ventilatory efficiency.
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Phillips, Devin B., James, Matthew D., Elbehairy, Amany F., Milne, Kathryn M., Vincent, Sandra G., Domnik, Nicolle J., de‐Torres, Juan P., Neder, J. Alberto, and O'Donnell, Denis E.
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OBSTRUCTIVE lung diseases , *EXERCISE tolerance , *CARBON monoxide , *AEROBIC capacity , *LUNG volume - Abstract
Background and objective: The combination of both reduced resting diffusing capacity of the lung for carbon monoxide (DLCO) and ventilatory efficiency (increased ventilatory requirement for CO2 clearance [V˙E/V˙CO2]) has been linked to exertional dyspnoea and exercise intolerance in chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are poorly understood. The current study examined if low resting DLCO and higher exercise ventilatory requirements were associated with earlier critical dynamic mechanical constraints, dyspnoea and exercise limitation in patients with mild COPD. Methods: In this retrospective analysis, we compared V˙E/V˙CO2, dynamic inspiratory reserve volume (IRV), dyspnoea and exercise capacity in groups of patients with Global Initiative for Chronic Obstructive Lung Disease stage 1 COPD with (1) a resting DLCO at or greater than the lower limit of normal (≥LLN; Global Lung Function Initiative reference equations [n = 44]) or (2) below the
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- 2021
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17. Deterioration of Nighttime Respiratory Mechanics in COPD: Impact of Bronchodilator Therapy.
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Domnik, Nicolle J., James, Matthew D., Scheeren, Robin E., Ayoo, Grace A., Taylor, Sarah M., Di Luch, Amanda T., Milne, Kathryn M., Vincent, Sandra G., Phillips, Devin B., Elbehairy, Amany F., Crinion, Sophie J., Driver, Helen S., Neder, J. Alberto, and O'Donnell, Denis E.
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RESPIRATORY mechanics , *OBSTRUCTIVE lung diseases , *AIRWAY (Anatomy) , *PLACEBOS , *RESEARCH , *ALKALOIDS , *RESEARCH methodology , *RESPIRATORY measurements , *MEDICAL cooperation , *EVALUATION research , *BRONCHODILATOR agents , *SLEEP , *DRUG administration , *COMPARATIVE studies , *RANDOMIZED controlled trials , *BLIND experiment , *FORCED expiratory volume , *RESEARCH funding , *SPIROMETRY , *CROSSOVER trials , *DISEASE complications - Abstract
Background: COPD is associated with nighttime respiratory symptoms, poor sleep quality, and increased risk of nocturnal death. Overnight deterioration of inspiratory capacity (IC) and FEV1 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. [ABSTRACT FROM AUTHOR]- Published
- 2021
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18. Dyspnea in COPD: New Mechanistic Insights and Management Implications.
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O'Donnell, Denis E., Milne, Kathryn M., James, Matthew D., de Torres, Juan Pablo, and Neder, J. Alberto
- Abstract
Dyspnea is the most common symptom experienced by patients with chronic obstructive pulmonary disease (COPD). To avoid exertional dyspnea, many patients adopt a sedentary lifestyle which predictably leads to extensive skeletal muscle deconditioning, social isolation, and its negative psychological sequalae. This "dyspnea spiral" is well documented and it is no surprise that alleviation of this distressing symptom has become a key objective highlighted across COPD guidelines. In reality, this important goal is often difficult to achieve, and successful symptom management awaits a clearer understanding of the underlying mechanisms of dyspnea and how these can be therapeutically manipulated for the patients' benefit. Current theoretical constructs of the origins of activity-related dyspnea generally endorse the classical demand-capacity imbalance theory. Thus, it is believed that disruption of the normally harmonious relationship between inspiratory neural drive (IND) to breathe and the simultaneous dynamic response of the respiratory system fundamentally shapes the expression of respiratory discomfort in COPD. Sadly, the symptom of dyspnea cannot be eliminated in patients with advanced COPD with relatively fixed pathophysiological impairment. However, there is evidence that effective symptom palliation is possible for many. Interventions that reduce IND, without compromising alveolar ventilation (VA), or that improve respiratory mechanics and muscle function, or that address the affective dimension, achieve measurable benefits. A common final pathway of dyspnea relief and improved exercise tolerance across the range of therapeutic interventions (bronchodilators, exercise training, ambulatory oxygen, inspiratory muscle training, and opiate medications) is reduced neuromechanical dissociation of the respiratory system. These interventions, singly and in combination, partially restore more harmonious matching of excessive IND to ventilatory output achieved. In this review we propose, on the basis of a thorough review of the recent literature, that effective dyspnea amelioration requires combined interventions and a structured multidisciplinary approach, carefully tailored to meet the specific needs of the individual. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
19. Low resting diffusion capacity, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease.
- Author
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Elbehairy, Amany F., O'Donnell, Conor D., Abd Elhameed, Asmaa, Vincent, Sandra G., Milne, Kathryn M., James, Matthew D., Webb, Katherine A., Neder, J. Alberto, and O'Donnell, Denis E.
- Subjects
OBSTRUCTIVE lung diseases ,PULMONARY gas exchange ,DYSPNEA ,EXERCISE tests ,RESPIRATORY mechanics - Abstract
The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (DL
CO ) to dyspnea and exercise intolerance across the chronic obstructive pulmonary disease (COPD) continuum are poorly understood. COPD progression generally involves both DLCO decline and worsening respiratory mechanics, and their relative contribution to dyspnea has not been determined. In a retrospective analysis of 300 COPD patients who completed symptom-limited incremental cardiopulmonary exercise tests, we tested the association between peak oxygen-uptake (VO2 ), DLCO , and other resting physiological measures. Then, we stratified the sample into tertiles of forced expiratory volume in 1 s (FEV1 ) and inspiratory capacity (IC) and compared dyspnea ratings, pulmonary gas exchange, and respiratory mechanics during exercise in groups with normal and low DLCO [i.e.,CO was associated with peak VO 2 (P = 0.006), peak work-rate (P = 0.005), and dyspnea/VO2 slope (P < 0.001) after adjustment for other independent variables (airway obstruction and hyperinflation). Within FEV1 and IC tertiles, peak VO2 and work rate were lower (P = 0.05) in low versus normal DLCO groups. Across all tertiles, low DLCO groups had higher dyspnea ratings, greater ventilatory inefficiency and arterial oxygen desaturation, and showed greater mechanical volume constraints at a lower ventilation during exercise than the normal DLCO group (all P < 0.05). After accounting for baseline resting respiratory mechanical abnormalities, DLCO CO. The higher dyspnea ratings and earlier exercise termination in low DL CO groups were linked to significantly greater pulmonary gas exchange abnormalities, higher ventilatory demand, and associated accelerated dynamic mechanical constraints. NEW & NOTEWORTHY Our study demonstrated that chronic obstructive pulmonary disease patients with diffusing capacity of the lung for carbon monoxide (DLCO ) less than the lower limit of normal had greater pulmonary gas exchange abnormalities, which resulted in higher ventilatory demand and greater dynamic mechanical constraints at lower ventilation during exercise. This, in turn, led to greater exertional dyspnea and exercise intolerance compared with patients with normal DLCO . [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
20. The Integrative Physiology of Exercise Training in Patients with COPD.
- Author
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Neder, J. Alberto, Marillier, Mathieu, Bernard, Anne-Catherine, James, Matthew D., Milne, Kathryn M., and O'Donnell, Denis E.
- Subjects
EXERCISE physiology ,PULMONARY gas exchange ,MUSCLE strength ,EXERCISE tolerance ,OBSTRUCTIVE lung diseases - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
21. Electronic Detection of Single-Base Mismatches in DNA with Ferrocene-Modified Probes.
- Author
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Yu, C.J., Yanjian Wan, Yowanto, Handy, Jie Li, Chunlin Tao, James, Matthew D., Tan, Christine L., Blackburn, Gary F., and Meade, Thomas J.
- Subjects
- *
DNA , *FERROCENE - Abstract
Investigates the electronic detection of single-base mismatches in DNA with ferrocene-modified probes. Importance of genotyping and gene-expression monitoring; Description of ferrocene-containing phosphoramidite; Analysis on thermal stability of metal containing DNA oligonucleotides.
- Published
- 2001
- Full Text
- View/download PDF
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