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BackgroundExercise tolerance is an important endpoint in chronic obstructive pulmonary disease (COPD) clinical trials. Little is known about the comparative measurement properties of constant work rate cycle ergometry (CWRCE) and the endurance shuttle walking test (ESWT). The objective of this sub-analysis of the TORRACTO® study was to directly compare the endurance measurement properties of CWRCE and ESWT in patients with COPD in a multicentre, multinational setting. We predicted that both tests would be similarly reliable, but that the ESWT would be more responsive to bronchodilation than CWRCE.MethodsThis analysis included 151 patients who performed CWRCE and ESWT at baseline and week 6 after receiving once-daily placebo, tiotropium/olodaterol (T/O) 2.5/5 μg or T/O 5/5 μg. Reproducibility was assessed by comparing their respective performance at baseline and week 6 in the placebo group. Responsiveness to bronchodilation was assessed by comparing endurance time at week 6 with T/O with baseline values and placebo. The locus of symptom limitation and end-exercise Borg scales for breathing and leg discomfort for both tests were also analysed.ResultsThe intraclass correlation coefficients for CWRCE and ESWT were 0.56 [95% confidence interval (CI) 0.37-0.71] and 0.75 (95% CI 0.63-0.84). More patients were limited by breathing discomfort during the ESWT than during CWRCE, whereas more patients were limited by leg discomfort or breathing/leg discomfort during CWRCE than the ESWT (p

BackgroundCOPD increases susceptibility to sleep disturbances, which may in turn predispose to increased respiratory symptoms. The objective of this study was to evaluate, in a population-based sample, the relationship between subjective sleep quality and risk of COPD exacerbations.MethodsData were obtained from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Participants with COPD who had completed 18 months of follow-up were included. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and a three-factor analysis. Symptom-based (dyspnea or sputum change ≥ 48 h) and event-based (symptoms plus medication or unscheduled health services use) exacerbations were assessed. Association of PSQI with exacerbation rate was assessed by using negative binomial regression. Exacerbation-free survival was also assessed.ResultsA total of 480 participants with COPD were studied, including 185 with one or more exacerbations during follow-up and 203 with poor baseline sleep quality (PSQI score > 5). Participants with subsequent symptom-based exacerbations had higher median baseline PSQI scores than those without (6.0 [interquartile range, 3.0-8.0] vs 5.0 [interquartile range, 2.0-7.0]; P = .01), and they were more likely to have baseline PSQI scores > 5 (50.3% vs 37.3%; P = .01). Higher PSQI scores were associated with increased symptom-based exacerbation risk (adjusted rate ratio, 1.09; 95% CI, 1.01-1.18; P = .02) and event-based exacerbation risk (adjusted rate ratio, 1.10; 95% CI, 1.00-1.21; P = .048). The association occurred mainly in those with undiagnosed COPD. Strongest associations were with Factor 3 (sleep disturbances and daytime dysfunction). Time to symptom-based exacerbation was shorter in participants with poor sleep quality (adjusted hazard ratio, 1.49; 95% CI, 1.09-2.03).ConclusionsHigher baseline PSQI scores were associated with increased risk of COPD exacerbation over 18 months' prospective follow-up.

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 FEV1 < 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]

BackgroundWe hypothesized that heterogeneity exists within the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 spirometric category and that different subgroups could be identified within this GOLD category.MethodsPre-randomization study participants from two clinical trials were symptomatic/asymptomatic GOLD 1 chronic obstructive pulmonary disease (COPD) patients and healthy controls. A hierarchical cluster analysis used pre-randomization demographics, symptom scores, lung function, peak exercise response and daily physical activity levels to derive population subgroups.ResultsConsiderable heterogeneity existed for clinical variables among patients with GOLD 1 COPD. All parameters, except forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC), had considerable overlap between GOLD 1 COPD and controls. Three-clusters were identified: cluster I (18 [15%] COPD patients; 105 [85%] controls); cluster II (45 [80%] COPD patients; 11 [20%] controls); and cluster III (22 [92%] COPD patients; 2 [8%] controls). Apart from reduced diffusion capacity and lower baseline dyspnea index versus controls, cluster I COPD patients had otherwise preserved lung volumes, exercise capacity and physical activity levels. Cluster II COPD patients had a higher smoking history and greater hyperinflation versus cluster I COPD patients. Cluster III COPD patients had reduced physical activity versus controls and clusters I and II COPD patients, and lower FEV1/FVC versus clusters I and II COPD patients.ConclusionsThe results emphasize heterogeneity within GOLD 1 COPD, supporting an individualized therapeutic approach to patients.Trial registrationwww.clinicaltrials.gov. NCT01360788 and NCT01072396.

BackgroundTo have a better understanding of the mechanisms of exercise limitation in mild-to-moderate chronic obstructive pulmonary disease (COPD), we compared detailed respiratory physiology in patients with COPD and healthy age- and sex-matched controls.MethodsData were collected during the pre-treatment, patient characterization phase of a multicenter, randomized, double-blind, crossover study. Patients with COPD met Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 spirometric criteria, were symptomatic, and had evidence of gas trapping during exercise. All participants completed pulmonary function and symptom-limited incremental treadmill exercise tests.ResultsChronic activity-related dyspnea measured by Baseline Dyspnea Index was similarly increased in patients with GOLD 1 (n = 41) and 2 (n = 63) COPD compared with controls (n = 104). Plethysmographic lung volumes were increased and lung diffusing capacity was decreased in both GOLD groups. Peak oxygen uptake and work rate were reduced in both GOLD groups compared with controls (p

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]

In people with COPD, pulmonary gas-exchange efficiency may be impaired because of abnormal alveolar ventilation (V˙A), capillary perfusion (Q˙c), or both. Both have been reported in early and mild stages of the disease. Such derangements often accompany significant clinical consequences such as activity-related dyspnea and exercise intolerance. Although much attention has been paid to pharmacologic treatment of mechanical abnormalities in COPD (eg, bronchodilators to deflate the lungs), increasing neurochemical afferent activity, secondary to gas-exchange inefficiency, has remained elusive as a therapeutic target. Hence, in this invited review, we first summarize how dyspnea, leading to poor exercise tolerance in COPD, may be explained by an increased venous admixture resulting from low V˙A/Q˙c, or wasted ventilation related to high V˙A/Q˙c, or both. We review the conflicting evidence supporting current treatments for gas-exchange inefficiency and exercise tolerance that act primarily on V˙A (bronchodilators, antiinflammatory medications) or Q˙c (oral and inhaled vasodilators, almitrine, and supplemental oxygen). Finally, to address the current knowledge and health care gaps, we propose two independent clinical research foci that may lead to a better understanding of the role of pulmonary gas-exchange inefficiency and activity-related dyspnea in COPD: (1) enhanced and deeper phenotyping of patients with COPD with V˙A/Q˙c abnormalities and (2) evaluation of existing and novel pharmacologic treatments to improve gas-exchange inefficiency, exertional dyspnea, and exercise tolerance across the spectrum of COPD severity. [ABSTRACT FROM AUTHOR]

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]

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 (...O2peak). 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]

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]

Purpose: To assess whether night-time increases in mechanical loading negatively impact respiratory muscle function in COPD and whether compensatory increases in inspiratory neural drive (IND) are adequate to stabilize ventilatory output and arterial oxygen saturation, especially during sleep when wakefulness drive is withdrawn. Methods: 21 patients with moderate-to-severe COPD and 20 age-/sex-matched healthy controls (CTRL) participated in a prospective, cross-sectional, one-night study to assess the impact of COPD on serial awake, supine inspiratory capacity (IC) measurements and continuous dynamic respiratory muscle function (esophageal manometry) and IND (diaphragm electromyography, EMGdi) in supine sleep. Results: Supine inspiratory effort and EMGdi were consistently twice as high in COPD versus CTRL (p < 0.05). Despite overnight increases in awake total airways resistance and dynamic lung hyperinflation in COPD (p < 0.05; not in CTRL), elevated awake EMGdi and respiratory effort were unaltered in COPD overnight. At sleep onset (non-rapid eye movement sleep, N2), EMGdi was decreased versus wakefulness in COPD (− 43 ± 36%; p < 0.05) while unaffected in CTRL (p = 0.11); however, respiratory effort and arterial oxygen saturation (SpO2) were unchanged. Similarly, in rapid eye movement (stage R), sleep EMGdi was decreased (− 38 ± 32%, p < 0.05) versus wakefulness in COPD, with preserved respiratory effort and minor (2%) reduction in SpO2. Conclusions: Despite progressive mechanical loading overnight and marked decreases in wakefulness drive, inspiratory effort and SpO2 were well maintained during sleep in COPD. Preserved high inspiratory effort during sleep, despite reduced EMGdi, suggests continued (or increased) efferent activation of extra-diaphragmatic muscles, even in stage R sleep. Clinical trial information: The COPD data reported herein were secondary data (Placebo arm only) obtained through the following Clinical Trial: "Effect of Aclidinium/Formoterol on Nighttime Lung Function and Morning Symptoms in Chronic Obstructive Pulmonary Disease" (https://clinicaltrials.gov/ct2/show/NCT02429765; NCT02429765). [ABSTRACT FROM AUTHOR]

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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Rationale: Although opioids are frequently prescribed in chronic obstructive pulmonary disease (COPD), there is poor understanding regarding which individuals will experience pulmonary harm upon exposure.Objectives: We sought to identify patient characteristics and opioid drug properties predictive of opioid-related adverse pulmonary events among older adults with chronic COPD.Methods: A retrospective, population-based, cohort study design was used, analyzing Ontario heath administrative data. Individuals aged 66 years and older, with validated, physician-diagnosed COPD receiving a new opioid drug were included. Adverse pulmonary events (defined as an emergency room visit, hospitalization, or death related to either COPD or pneumonia) occurring within 30 days following new opioid receipt were considered. Multivariable-adjusted, cause-specific hazard modeling was used to identify predictors of adverse pulmonary events.Results: Out of 169,517 older adults with COPD receiving a new opioid, 4,861 (2.9%) experienced an adverse pulmonary event within 30 days. Factors independently predisposing to adverse pulmonary events included older age (≥85 yr old: hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.26-1.49), long-term-care home residence (HR, 1.32; 95% CI, 1.21-1.44), severe COPD exacerbation within the preceding year (HR, 2.96; 95% CI, 2.77-3.17), comorbidities (including non-COPD lung disease [HR, 1.16; 95% CI, 1.09-1.23], congestive heart failure [HR, 1.22; 95% CI, 1.14-1.30], sleep disorder [HR, 1.22; 95% CI, 1.15-1.30], and dementia [HR, 1.14; 95% CI, 1.05-1.24]); other psychoactive medication receipt, including benzodiazepines (HR, 1.27; 95% CI, 1.19-1.35) and serotonergic antidepressants (HR, 1.10; 95% CI, 1.03-1.19), and receipt of an opioid-only agent (HR, 1.35; 95% CI, 1.26-1.46). Factors that independently protected from adverse pulmonary events included female sex (HR, 0.78; 95% CI, 0.73-0.82), surgery within the preceding year (HR, 0.70; 95% CI, 0.64-0.77), and musculoskeletal disease (HR, 0.75; 95% CI, 0.70-0.80). No significant associations were observed between adverse pulmonary events and opioid half-life duration or opioid daily dosage.Conclusions: Patient and opioid drug factors predictive of opioid-related adverse pulmonary events among older adults with COPD were identified, which may assist with safer opioid prescribing. [ABSTRACT FROM AUTHOR]

Dyspnoea (perceived breathing discomfort) is the most common symptom experienced by patients with chronic obstructive pulmonary disease (COPD) and is associated with progressive physical inactivity and poor quality of life. Exertional dyspnoea ratings in COPD have been shown to consistently correlate with a number of physiological ratios that ultimately point to demand/capacity imbalance of the dynamic respiratory system.[1] These include ventilatory output, tidal oesophageal pressure and tidal diaphragmatic electromyography (EMG) (all expressed relative to respective maxima). Studies using bronchodilators or inspiratory muscle training (IMT) to relive dyspnoea have confirmed the importance of high IND in dyspnoea causation in COPD. [Extracted from the article]

Among patients with chronic obstructive pulmonary disease (COPD), those with the lowest maximal inspiratory pressures experience greater breathing discomfort (dyspnea) during exercise. In such individuals, inspiratory muscle training (IMT) may be associated with improvement of dyspnea, but the mechanisms for this are poorly understood. Therefore, we aimed to identify physiological mechanisms of improvement in dyspnea and exercise endurance following inspiratory muscle training (IMT) in patients with COPD and low maximal inspiratory pressure (Pimax). The effects of 8 wk of controlled IMT on respiratory muscle function, dyspnea, respiratory mechanics, and diaphragm electromyography (EMGdi) during constant work rate cycle exercise were evaluated in patients with activity-related dyspnea (baseline dyspnea index <9). Subjects were randomized to either IMT or a sham training control group (n = 10 each). Twenty subjects (FEV1 = 47 ± 19% predicted; Pimax  = −59 ± 14 cmH2O; cycle ergometer peak work rate = 47 ± 21% predicted) completed the study; groups had comparable baseline lung function, respiratory muscle strength, activity-related dyspnea, and exercise capacity. IMT, compared with control, was associated with greater increases in inspiratory muscle strength and endurance, with attendant improvements in exertional dyspnea and exercise endurance time (all P < 0.05). After IMT, EMGdi expressed relative to its maximum (EMGdi/EMGdimax) decreased (P < 0.05) with no significant change in ventilation, tidal inspiratory pressures, breathing pattern, or operating lung volumes during exercise. In conclusion, IMT improved inspiratory muscle strength and endurance in mechanically compromised patients with COPD and low Pimax. The attendant reduction in EMGdi/EMGdimax helped explain the decrease in perceived respiratory discomfort despite sustained high ventilation and intrinsic mechanical loading over a longer exercise duration. NEW & NOTEWORTHY In patients with COPD and low maximal inspiratory pressures, inspiratory muscle training (IMT) may be associated with improvement of dyspnea, but the mechanisms for this are poorly understood. This study showed that 8 wk of home-based, partially supervised IMT improved respiratory muscle strength and endurance, dyspnea, and exercise endurance. Dyspnea relief occurred in conjunction with a reduced activation of the diaphragm relative to maximum in the absence of significant changes in ventilation, breathing pattern, and operating lung volumes. [ABSTRACT FROM AUTHOR]

AIMS Diuretic drugs may theoretically improve respiratory health outcomes in chronic obstructive pulmonary disease (COPD) through several possible mechanisms, but they might also lead to respiratory harm. We evaluated the association of incident oral diuretic drug use with respiratory-related morbidity and mortality among older adults with COPD. METHODS This was a population-based, retrospective cohort study using health administrative data from Ontario, Canada, for the period 2008–2013. We identified adults aged 66 years and older with nonpalliative COPD using a validated algorithm. Respiratoryrelated morbidity and mortality were evaluated within 30 days of incident oral diuretic drug use compared to nonuse using Cox proportional hazard regression and applying inverse probability of treatment weighting using the propensity score to minimize confounding. RESULTS Out of 99 766 individuals aged 66 years and older with COPD identified, incident diuretic receipt occurred in 51.7%. Relative to controls, incident diuretic users had significantly increased rates for hospitalization for COPD or pneumonia [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.07–1.40], as well as more emergency room visits for COPD or pneumonia (HR 1.35, 95% CI 1.18–1.56), COPD or pneumonia-related mortality (HR 1.41; 95% CI 1.04–1.92) and all-cause mortality (HR 1.20, 95% CI 1.06–1.35). The increased respiratory-related morbidity and mortality observed were specifically as a result of loop diuretic use. CONCLUSIONS Incident diuretic drugs, and more specifically loop diuretics, were associated with increased rates of respiratory-related morbidity andmortality among older adults with nonpalliative COPD. Further studies are needed to determine if this association is causative or due to unresolved confounding. [ABSTRACT FROM AUTHOR]

Rationale: An increased ventilatory response to exertional metabolic demand (high [Formula: see text]e/[Formula: see text]co2 relationship) is a common finding in patients with coexistent chronic obstructive pulmonary disease and heart failure.Objectives: We aimed to determine the mechanisms underlying high [Formula: see text]e/[Formula: see text]co2 and its impact on operating lung volumes, dyspnea, and exercise tolerance in these patients.Methods: Twenty-two ex-smokers with combined chronic obstructive pulmonary disease and heart failure with reduced left ventricular ejection fraction undertook, after careful treatment optimization, a progressive cycle exercise test with capillary (c) blood gas collection.Measurements and Main Results: Regardless of the chosen metric (increased [Formula: see text]e-[Formula: see text]co2 slope, [Formula: see text]e/[Formula: see text]co2 nadir, or end-exercise [Formula: see text]e/[Formula: see text]co2), ventilatory inefficiency was closely related to PcCO2 (r values from -0.80 to -0.84; P < 0.001) but not dead space/tidal volume ratio. Ten patients consistently maintained exercise PcCO2 less than or equal to 35 mm Hg (hypocapnia). These patients had particularly poor ventilatory efficiency compared with patients without hypocapnia (P < 0.05). Despite the lack of between-group differences in spirometry, lung volumes, and left ventricular ejection fraction, patients with hypocapnia had lower resting PaCO2 and lung diffusing capacity (P < 0.01). Excessive ventilatory response in this group was associated with higher exertional PcO2. The group with hypocapnia, however, had worse mechanical inspiratory constraints and higher dyspnea scores for a given work rate leading to poorer exercise tolerance compared with their counterparts (P < 0.05).Conclusions: Heightened neural drive promoting a ventilatory response beyond that required to overcome an increased "wasted" ventilation led to hypocapnia and poor exercise ventilatory efficiency in chronic obstructive pulmonary disease-heart failure overlap. Excessive ventilation led to better arterial oxygenation but at the expense of earlier critical mechanical constraints and intolerable dyspnea. [ABSTRACT FROM AUTHOR]

Exertional dyspnea is present across the spectrum of chronic obstructive pulmonary disease (COPD) severity. However, without realizing it themselves, patients may decrease daily physical activity to avoid distressing respiratory sensations. Dyspnea also may be associated with deconditioning. Cardiopulmonary exercise testing can uncover exertional dyspnea and its physiological determinants in patients with preserved or only mildly reduced FEV1. Dyspnea in mild COPD can largely be explained by increased "wasted" ventilation in the physiological dead space, which heightens the drive to breathe and worsens the inspiratory mechanical constraints. During incremental exercise testing, this is readily identified as an excessive ventilation-to-metabolic demand, that is, a high ventilation ([Formula: see text]e) to carbon dioxide output ([Formula: see text]co2) relationship. Linking increases in [Formula: see text]e/[Formula: see text]co2 to exertional dyspnea may provide objective evidence that a patient's poor exercise tolerance is not just a consequence of deconditioning. This information should prompt a proactive therapeutic approach to increase the available ventilatory reserve by, for example, giving inhaled bronchodilators. Considering that the structural determinants of ventilatory inefficiency (early emphysema, ventilation-perfusion mismatching, and microvascular disease) may progress despite only modest changes in FEV1, serial [Formula: see text]e/[Formula: see text]co2 measurements might also prove valuable to track disease progression in these symptomatic patients. [ABSTRACT FROM AUTHOR]

Low inspiratory capacity (IC), chronic dyspnea, and reduced exercise capacity are inextricably linked and are independent predictors of increased mortality in chronic obstructive pulmonary disease. It is no surprise, therefore, that a major goal of management is to improve IC by reducing lung hyperinflation to improve respiratory symptoms and health-related quality of life. The negative effects of lung hyperinflation on respiratory muscle and cardiocirculatory function during exercise are now well established. Moreover, there is growing appreciation that a key mechanism of exertional dyspnea in chronic obstructive pulmonary disease is critical mechanical constraints on tidal volume expansion during exercise when resting IC is reduced. Further evidence for the importance of lung hyperinflation comes from multiple studies, which have reported the clinical benefits of therapeutic interventions that reduce lung hyperinflation and increase IC. A reduced IC in obstructive pulmonary disease is further eroded by exercise and contributes to ventilatory limitation and dyspnea. It is an important outcome for both clinical and research studies. [ABSTRACT FROM AUTHOR]

Dyspnea and exercise limitation are among the most common symptoms experienced by patients with various chronic lung diseases and are linked to poor quality of life. Our understanding of the source and nature of perceived respiratory discomfort and exercise intolerance in chronic lung diseases has increased substantially in recent years. These new mechanistic insights are the primary focus of the current review. Cardiopulmonary exercise testing (CPET) provides a unique opportunity to objectively evaluate the ability of the respiratory system to respond to imposed incremental physiological stress. In addition to measuring aerobic capacity and quantifying an individual's cardiac and ventilatory reserves, we have expanded the role of CPET to include evaluation of symptom intensity, together with a simple "non-invasive" assessment of relevant ventilatory control parameters and dynamic respiratory mechanics during standardized incremental tests to tolerance. This review explores the application of the new advances in the clinical evaluation of the pathophysiology of exercise intolerance in chronic obstructive pulmonary disease (COPD), chronic asthma, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). We hope to demonstrate how this novel approach to CPET interpretation, which includes a quantification of activity-related dyspnea and evaluation of its underlying mechanisms, enhances our ability to meaningfully intervene to improve quality of life in these pathologically-distinct conditions. [ABSTRACT FROM AUTHOR]

Background: Thoracic computed tomography (CT) scans are widely performed in clinical practice, often leading to detection of airway or parenchymal abnormalities in asymptomatic or minimally symptomatic individuals. However, clinical relevance of CT abnormalities is uncertain in the general population. Methods: We evaluated data from 1361 participants aged ≥40 years from a Canadian prospective cohort comprising 408 healthy never-smokers, 502 healthy ever-smokers, and 451 individuals with spirometric evidence of chronic obstructive pulmonary disease (COPD) who had thoracic CT scans. CT images of subjects were visually scored for respiratory bronchiolitis(RB), emphysema(E), bronchial-wall thickening(BWT), expiratory air-trapping(AT), and bronchiectasis(B). Multivariable logistic regression models were used to assess associations of CT features with respiratory symptoms, dyspnea, health status as determined by COPD assessment test, and risk of clinically significant exacerbations during 12 months follow-up. Results: About 11% of life-time never-smokers demonstrated emphysema on CT scans. Prevalence increased to 30% among smokers with normal lung function and 36%, 50%, and 57% among individuals with mild, moderate or severe/very severe COPD, respectively. Presence of emphysema on CT was associated with chronic cough (OR,2.11; 95%CI,1.4–3.18); chronic phlegm production (OR,1.87; 95% CI,1.27–2.76); wheeze (OR,1.61; 95% CI,1.05–2.48); dyspnoea (OR,2.90; 95% CI,1.41–5.98); CAT score≥10(OR,2.17; 95%CI,1.42–3.30) and risk of ≥2 exacerbations over 12 months (OR,2.17; 95% CI, 1.42–3.0). Conclusions: Burden of thoracic CT abnormalities is high among Canadians ≥40 years of age, including never-smokers and smokers with normal lung function. Detection of emphysema on CT scans is associated with pulmonary symptoms and increased risk of exacerbations, independent of smoking or lung function. [ABSTRACT FROM AUTHOR]

Rationale: The mechanisms underlying dyspnea in interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD) are unknown.Objectives: To examine whether the relationship between inspiratory neural drive to the diaphragm and exertional dyspnea intensity is different in ILD and COPD, given the marked differences in static respiratory mechanics between these conditions.Methods: We compared sensory-mechanical relationships in patients with ILD, patients with COPD, and healthy control subjects (n = 16 each) during incremental cycle exercise with diaphragmatic electromyography (EMGdi) and respiratory pressure measurements.Measurements and Main Results: In patients with mild to moderate ILD or COPD with similarly reduced inspiratory capacity, the peak oxygen uptake, work rate, and ventilation were lower (P < 0.05) than in healthy control subjects. EMGdi expressed as a percentage of the maximum (EMGdi/EMGdi,max), respiratory effort (esophageal pressure expressed as percentage of the maximum), and ventilation were higher (P < 0.05) at rest and during exercise in both patients with ILD and patients with COPD than in control subjects. Each of these measurements was similar in the ILD and COPD groups. A Vt inflection and critically reduced inspiratory reserve volume occurred at a lower (P < 0.05) ventilation in the ILD and COPD groups than in control subjects. Patients with ILD had greater diaphragmatic activity, whereas patients with COPD had greater expiratory muscle activity. The relationship between dyspnea intensity and EMGdi/EMGdi,max during exercise was similar in all three groups. In ILD and COPD, descriptors alluding to inspiratory difficulty were selected more frequently, with a greater disparity between EMGdi/EMGdi,max and Vt.Conclusions: Disease-specific differences in mechanics and respiratory muscle activity did not influence the key association between dyspnea intensity and inspiratory neural drive to the diaphragm. [ABSTRACT FROM AUTHOR]

Impairment in oxygen (O2) delivery to the central nervous system ("brain") and skeletal locomotor muscle during exercise has been associated with central and peripheral neuromuscular fatigue in healthy humans. From a clinical perspective, impaired tissue O2 transport is a key pathophysiological mechanism shared by cardiopulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). In addition to arterial hypoxemic conditions in COPD, there is growing evidence that cerebral and muscle blood flow and oxygenation can be reduced during exercise in both isolated COPD and CHF. Compromised cardiac output due to impaired cardiopulmonary function/interactions and blood flow redistribution to the overloaded respiratory muscles (i.e., ↑work of breathing) may underpin these abnormalities. Unfortunately, COPD and CHF coexist in almost a third of elderly patients making these mechanisms potentially more relevant to exercise intolerance. In this context, it remains unknown whether decreased O2 delivery accentuates neuromuscular manifestations of central and peripheral fatigue in coexistent COPD-CHF. If this holds true, it is conceivable that delivering a low-density gas mixture (heliox) through non-invasive positive pressure ventilation could ameliorate cardiopulmonary function/interactions and reduce the work of breathing during exercise in these patients. The major consequence would be increased O2 delivery to the brain and active muscles with potential benefits to exercise capacity (i.e., ↓central and peripheral neuromuscular fatigue, respectively). We therefore hypothesize that patients with coexistent COPD-CHF stop exercising prematurely due to impaired central motor drive and muscle contractility as the cardiorespiratory system fails to deliver sufficient O2 to simultaneously attend the metabolic demands of the brain and the active limb muscles. [ABSTRACT FROM AUTHOR]

The purpose of this exploratory physiological study was to evaluate the effects of inhaled fluticasone/salmeterol combination (FSC) on sensory and physiological responses to exercise in subjects with mild-to-moderate COPD. In a randomized, double-blind, placebo-controlled, crossover study, subjects underwent 6-week treatments with FSC or placebo (PLA). Detailed pulmonary function and constant-work rate cycle exercise tests were performed following each treatment period. Fifteen subjects completed the study (mean ± SD): age 64 ± 10 years; smoking history 47 ± 29 pack-years; post-bronchodilator forced expiratory volume in 1 s86± 15%predicted (10 mild and 5 mod-erate COPD); peak incremental oxygen uptake 71 ± 16%predicted. Compared with PLA, FSC treatment was associated with improved: FEV1 by 0.23 ± 0.18 L; inspiratory capacity by 0.18 ± 0.23 L; functional residual capacity by -0.28 ± 0.30 L; and specific airways resistance by -4.6 ±4.5 cmH2O s (all p < 0.01). There were no significant changes in dyspnea intensity throughout exercise and endurance time did not change significantly (1.2 ± 3.0 min, p = 0.149). Following FSC, inspiratory capacity at rest and throughout exercise increased by 0.2-0.3 L with concomitant increases in tidal volume and ventilation (p < 0.05). Compared with PLA, the work of breathing and the ratio of respiratory muscle effort to tidal volume improved with FSC during exercise (p < 0.05). In mild-to-moderate COPD, FSC was associated with significant improvements in airway function at rest and during exercise. Despite important mechanical improvements, there were no significant effects on dyspnea intensity and exercise endurance. [ABSTRACT FROM AUTHOR]

Summary: Rationale: Combination therapy with corticosteroid and long-acting β2-agonists (LABA) in a single inhaler is associated with superior effects on airway function and exercise performance in COPD compared with LABA monotherapy. The physiological effects of adding inhaled corticosteroid monotherapy to maintenance bronchodilator therapy (long-acting anticholinergics and LABA singly or in combination) in COPD are unknown. Methods: This was a randomized, double-blind, placebo-controlled, crossover study (NCT00387036) to compare the effects of inhaled fluticasone propionate 500 μg (FP500) twice-daily and placebo (PLA) on airway function during rest and exercise, measured during constant work rate cycle exercise at 75% of maximum incremental cycle work rate, in 17 patients with COPD (FEV1 ≤ 70% predicted). Results: After treatment with FP500 compared to PLA, there were significant increases in post-dose measurements of FEV1 (+115 mL, P = 0.006) and the FEV1/FVC ratio (+2.5%, P = 0.017), along with decreases in plethysmographic residual volume (−0.32L; P = 0.031), functional residual capacity (−0.30L, P = 0.033), and total lung capacity (−0.30L, P = 0.027) but no changes in vital capacity or inspiratory capacity (IC). Post-treatment comparisons demonstrated a significant improvement in endurance time by 188 ± 362 s with FP500 (P = 0.047) with no concomitant increase in dyspnea intensity. End-inspiratory and end-expiratory lung volumes were reduced at rest and throughout exercise with FP500 compared with PLA (P < 0.05). Conclusion: Inhaled FP500 monotherapy was associated with consistent and clinically important improvements in FEV1, static lung volumes, dynamic operating lung volumes, and exercise endurance when added to established maintenance long-acting bronchodilator therapy in patients with moderate to severe COPD. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide and most of those afflicted have mild to moderate disease as measured by spirometry. There is mounting evidence that even mild airway obstruction is associated with activity-related dyspnea, exercise limitation, impaired quality of life, increased hospitalization and mortality. As our understanding of the complex, heterogeneous pathophysiology and clinical consequences of milder COPD continues to grow, there is increasing interest in the potential impact of therapeutic interventions beyond smoking cessation. Unfortunately, few clinical trials have included patients with mild to moderate disease and the evidence base for pharmacological treatment in this subpopulation is currently lacking. Recent short-term mechanistic studies confirm that reversal of airway smooth muscle cholinergic tone consistently improves respiratory mechanics during rest and exercise in mild COPD but long-term clinical benefits remain to be evaluated. Secondary analysis of large, prospective studies designed to evaluate the efficacy of long-acting bronchodilators, inhaled corticosteroids and combination therapy indicate that patients with moderate COPD achieve comparable benefits to those with advanced disease. In the absence of evidence-based guidelines for the management of milder COPD, treatment choices are driven mainly by clinical presentation: for those with persistent and troublesome activity-related dyspnea a trial of inhaled bronchodilator therapy is justified; for those with a propensity for recurrent infective exacerbations, consideration of additional anti-inflammatory treatment seems reasonable. In this paper, we review the current knowledge base and emerging paradigm for the pharmacological treatment of mild to moderate COPD. [ABSTRACT FROM PUBLISHER]

We aimed to characterize gender differences in exercise endurance, operating lung volumes and symptoms limitation during exercise in patients with COPD. Ninety-three women and 93 men with COPD matched for age and disease severity were evaluated during symptom-limited constant-work rate cycle exercise at 75% of peak capacity. Breathing pattern, inspiratory capacity, dyspnoea and leg discomfort Borg scores were recorded during exercise. Endurance time was shorter in women compared to men. Inspiratory capacity decreased at a similar rate during exercise in women and men (0.71 vs. 0.81 ml· s- 1 for women and men respectively, p = 0.47) despite lower ventilation at end-exercise in women. At end-exercise, women showed lower inspiratory reserve volume (p < 0.005). Dyspnoea responses during exercise occurred with a steep rise near end-exercise, when inspiratory reserve volume approached a critical value, at 10% of total lung capacity, this onset of dyspnoea acceleration occurred earlier in women (p < 0.0001). At the same relative exercise intensity, women with COPD had lower endurance time than men. Compared to men, women with COPD were disadvantaged during exercise as they reached a critical inspiratory reserve volume earlier, leading to a steep increase in dyspnoea and to exercise termination. [ABSTRACT FROM AUTHOR]

Abstract: Progressive activity-related dyspnea dominates the clinical presentation of patients afflicted by chronic obstructive and restrictive lung diseases. This symptom invariably leads to activity limitation, global skeletal muscle deconditioning and an impoverished quality of life. The effective management of exertional dyspnea remains an elusive goal but our understanding of the nature and mechanisms of this distressing symptom continues to grow. Refinements in psychophysical measurement of the sensory intensity and quality of dyspnea during laboratory clinical cardiopulmonary exercise testing (CPET) have provided new insights into causation. In this review, we focus on what is known about the physiological mechanisms of dyspnea during physical exertion in patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Although these conditions are pathologically diverse, perceptual and ventilatory responses to exercise are remarkably similar among patients with these two conditions. In both patient groups, dyspnea intensity is increased at any given ventilation compared with age-matched healthy individuals; at the limits of tolerance, most patients predominantly select qualitative descriptors that allude to perceptions of “increased respiratory effort” and “unsatisfied inspiration.” Common abnormal physiological responses to CPET across conditions include: (1) increased central respiratory drive secondary to pulmonary gas exchange and metabolic derangements, (2) abnormal “restrictive” constraints on tidal volume expansion with earlier development of critical mechanical limitation of ventilation and (3) an increasing disparity (as exercise proceeds) between the magnitude of contractile respiratory muscle effort and the thoracic volume displacement achieved. Reductionist experimental approaches that attempt to partition, or isolate, the contribution of central and multiple peripheral sensory afferent systems to activity-induced dyspnea have met with limited success. Integrative approaches which explore the possible neurophysiological mechanisms involved in the two dominant qualitative descriptors of activity-related dyspnea in both diseases may prove to be more fruitful. In this review, we present a hypothetical model for exertional dyspnea that is based on current neurophysiological constructs that have been rigorously developed to explain the origins of perceptions of “effort,” “air hunger” and the accompanying affective “distress” response. [Copyright &y& Elsevier]

During constant-work-rate exercise in chronic obstructive pulmonary disease, dyspnea increases steeply once inspiratory reserve volume (IRV) falls to a critical level that prevents further expansion of tidal volume (VT). We studied the effects of this mechanical restriction on the quality and intensity of exertional dyspnea and examined the impact of an anti-cholinergic bronchodilator. In a randomized, double-blind, crossover study, 18 patients with chronic obstructive pulmonary disease (forced expiratory volume in 1 s = 40 ± 3%predicted; mean ± SE) inhaled tiotropium 18 μg or placebo once daily for 7–10 days each. Pulmonary function tests and symptom-limited cycle exercise at 75% of each patient's maximal work capacity were performed 2 h after dosing. Dyspnea intensity (Borg scale), operating lung volumes, breathing pattern, and esophageal pressure (n = 11) were measured during exercise. Dynamic hyperinflation reached its maximal value early in exercise and was associated with only mild increases in dyspnea intensity and the effort-displacement ratio, which is defined as the ratio between tidal swings of esophageal pressure (expressed relative to maximum inspiratory pressure) and VT (expressed relative to predicted vital capacity). After a minimal IRV of 0.5 ± 0.1 liter was reached, both dyspnea and the effort-displacement ratio rose steeply until an intolerable level was reached. Tiotropium did not alter dyspnea-IRV relationships, but the increase in resting and exercise inspiratory capacity was associated with an improved effort-displacement ratio throughout exercise. Once a critically low IRV was reached during exercise, dyspnea rose with the disparity between respiratory effort and the VT response. Changes in dyspnea intensity after tiotropium were positively correlated with changes in this index of neuromechanical coupling. [ABSTRACT FROM AUTHOR]

Cerebral blood flow (CBF) and oxygenation (COx) are generally well-preserved in COPD. It is unknown whether prevalent cardiovascular co-morbidities, such as heart failure, may impair CBF and COx responses to exertion. Eighteen males with moderate-to-severe COPD (8 with and 10 without overlapping heart failure) underwent a progressive exercise test with pre-frontal CBF and COx measurements (indocyanine green and near-infrared spectroscopy). Mean arterial pressure and cardiac output were lower from rest to exercise in overlap. Only COPD patients demonstrated an increase in arterialized PCO 2 towards the end of progressive exercise. CBF index was consistently higher and increased further by ∼40% during exercise in COPD whereas a ∼10% reduction was observed in overlap. COx was lower in overlap despite preserved arterial oxygenation. In conclusion, heart failure introduces pronounced negative effects on CBF and COx in COPD which may be associated with clinically relevant outcomes, including dyspnea, exercise intolerance, cerebrovascular disease and cognitive impairment. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to evaluate the physiological basis for sex-differences in exercise-induced dyspnea in patients with mild COPD. We compared operating lung volumes, breathing pattern and dyspnea during incremental cycling in 32 men (FEV1 =86±10% predicted) and women (FEV1 =86±12% predicted) with mild COPD and 32 age-matched controls. There were no sex differences in dyspnea in the control group at any work-rate or ventilation (). Women with COPD had significantly greater dyspnea than men at 60 and 80W. At 80W, dyspnea ratings were 5.7±2.3 and 3.3±2.5Borg units (P <0.05) and the to maximal ventilatory capacity ratio was 72% and 55% in women and men, respectively (P <0.05). Comparable increases in dynamic hyperinflation were seen in both male and female COPD groups at symptom limitation but women reached tidal volume constraints at a lower work rate and than men. Superimposing mild COPD on the normal aging effects had greater sensory consequences in women because of their naturally reduced ventilatory reserve. [Copyright &y& Elsevier]