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Heightened sensation of leg effort contributes importantly to poor exercise tolerance in patient populations. We aim to provide a sex‐ and age‐adjusted frame of reference to judge symptom's normalcy across progressively higher exercise intensities during incremental exercise. Two‐hundred and seventy‐five non‐trained subjects (130 men) aged 19–85 prospectively underwent incremental cycle ergometry. After establishing centiles‐based norms for Borg leg effort scores (0–10 category‐ratio scale) versus work rate, exponential loss function identified the centile that best quantified the symptom's severity individually. Peak O2 uptake and work rate (% predicted) were used to threshold gradually higher symptom intensity categories. Leg effort‐work rate increased as a function of age; women typically reported higher scores at a given age, particularly in the younger groups (p < 0.05). For instance, "heavy" (5) scores at the 95th centile were reported at ~200 W (<40 years) and ~90 W (≥70 years) in men versus ~130 W and ~70 W in women, respectively. The following categories of leg effort severity were associated with progressively lower exercise capacity: ≤50th ("mild"), >50th to <75th ("moderate"), ≥75th to <95th ("severe"), and ≥ 95th ("very severe") (p < 0.05). Although most subjects reporting peak scores <5 were in "mild" range, higher scores were not predictive of the other categories (p > 0.05). This novel frame of reference for 0–10 Borg leg effort, which considers its cumulative burden across increasingly higher exercise intensities, might prove valuable to judging symptom's normalcy, quantifying its severity, and assessing the effects of interventions in clinical populations. [ABSTRACT FROM AUTHOR]

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 (DLCO < 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]

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]

Background: Reduced exercise capacity has been reported previously in patients with OSA hypopnea syndrome (OSAHS), although the underlying mechanisms are unclear.Research Question: What are the underlying mechanisms of reduced exercise capacity in untreated patients with OSAHS? Is there a role for systemic or pulmonary vascular abnormalities?Study Design and Methods: This was a cross-sectional observational study in which 14 patients with moderate to severe OSAHS and 10 control participants (matched for age, BMI, smoking history, and FEV1) underwent spirometry, incremental cycle cardiopulmonary exercise testing (CPET) with arterial line, resting echocardiography, and assessment of arterial stiffness (pulse wave velocity [PWV] and augmentation index [AIx]).Results: Patients (mean ± SD age, 50 ± 11 years; mean ± SD BMI, 30.5 ± 2.7 kg/m2; mean ± SD smoking history, 2.4 ± 4.0 pack-years; mean ± SD FEV1 to FVC ratio, 0.78 ± 0.04%; mean ± SD FEV1, 85 ± 14% predicted) showed mean ± SD apnea hypopnea index of 43 ± 19/h. At rest, PWV, AIx, and mean pulmonary artery pressure (PAP) were higher in patients vs control participants (P < .05). During CPET, patients showed lower peak work rate (WR) and oxygen uptake and greater dyspnea ratings compared with control participants (P < .05 for all). Minute ventilation (V·E), ventilatory equivalent for CO2 output (V·E/V·CO2), and dead space ventilation (VD) to tidal volume (VT) ratio were greater in patients vs control participants during exercise (P < .05 for all). Reduction in VD to VT ratio from rest to peak exercise was greater in control participants compared with patients (0.24 ± 0.08 vs 0.04 ± 0.14, respectively; P = .001). Dyspnea intensity at the highest equivalent WR correlated with corresponding values of V·E/V·CO2 (r = 0.65; P = .002), and VD (r = 0.70; P = .001). Age, PWV, and mean PAP explained approximately 70% of the variance in peak WR, whereas predictors of dyspnea during CPET were rest-to-peak change in VD to VT ratio and PWV (R2 = 0.50; P < .001).Interpretation: Patients with OSAHS showed evidence of pulmonary gas exchange abnormalities during exercise (in the form of increased dead space) and resting systemic vascular dysfunction that may explain reduced exercise capacity and increased exertional dyspnea intensity. [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]

A cardiopulmonary exercise test (CPET) is ideally suited to quantify exercise tolerance and evaluate the pathophysiological mechanism(s) of dyspnea and exercise limitation in people with chronic respiratory disease. Although there are several statements on CPET and many outstanding resources detailing the cardiorespiratory and perceptual responses to exercise, limited information is available to support the health care provider in conducting a practical CPET evaluation. This article provides the health care provider with practical and timely information on how to use CPET data to understand dyspnea and exercise intolerance in people with chronic respiratory diseases. Information on CPET protocol, as well as how to evaluate maximal patient effort, peak rate of oxygen consumption, ventilatory demand, pulmonary gas exchange, ventilatory reserve, operating lung volumes, and exertional dyspnea, is presented. Two case examples are also described to highlight how these parameters are evaluated to provide a clinical interpretation of CPET data. [ABSTRACT FROM AUTHOR]

Background: Exercise-induced hypoxaemia is a hallmark of chronic fibrotic interstitial lung disease (f-ILD). It remains unclear whether patients' severe hypoxaemia may exaggerate locomotor muscle fatigue and, if so, to what extent oxygen (O2) supplementation can ameliorate these abnormalities.Methods: Fifteen patients (12 males, 9 with idiopathic pulmonary fibrosis) performed a constant-load (60% peak work rate) cycle test to symptom limitation (Tlim) while breathing medical air. Fifteen age-matched and sex-matched controls cycled up to patients' Tlim. Patients repeated the exercise test on supplemental O2 (42%±7%) for the same duration. Near-infrared spectroscopy assessed vastus lateralis oxyhaemoglobin concentration ((HbO2)). Pre-exercise to postexercise variation in twitch force (∆Tw) induced by femoral nerve magnetic stimulation quantified muscle fatigue.Results: Patients showed severe hypoxaemia (lowest O2 saturation by pulse oximetry=80.0%±7.6%) which was associated with a blunted increase in muscle (HbO2) during exercise vs controls (+1.3±0.3 µmol vs +4.4±0.4 µmol, respectively; p<0.001). Despite exercising at work rates ∼ one-third lower than controls (42±13 W vs 66±13 W), ∆Tw was greater in patients (∆Tw/external work performed by the leg muscles=-0.59±0.21 %/kJ vs -0.25±0.19 %/kJ; p<0.001). Reversal of exertional hypoxaemia with supplemental O2 was associated with a significant increase in muscle (HbO2), leading to a reduced decrease in ∆Tw in patients (-0.33±0.19 %/kJ; p<0.001 vs air). Supplemental O2 significantly improved leg discomfort (p=0.005).Conclusion: O2 supplementation during exercise improves leg muscle oxygenation and fatigue in f-ILD. Lessening peripheral muscle fatigue to enhance exercise tolerance is a neglected therapeutic target that deserves clinical attention in this patient population. [ABSTRACT FROM AUTHOR]

Background: Physiologic and symptom responses at the ventilatory threshold (Tvent) during incremental cardiopulmonary exercise testing (CPET) can provide important prognostic information.Research Question: This study aimed to develop an updated normative reference set for physiologic and symptom responses at Tvent during cycle CPET (primary aim) and to evaluate previously recommended reference equations from a 1985 study for predicting Tvent responses (secondary aim).Study Design and Methods: Participants were adults 40 to 80 years of age who were free of clinically relevant disease from the Canadian Cohort Obstructive Lung Disease. Rate of oxygen consumption (V˙O2) at Tvent was identified by two independent raters; physiologic and symptom responses corresponding to V˙O2 at Tvent were identified by linear interpolation. Reference ranges (5th-95th percentiles) for responses at Tvent were calculated according to participant sex and age for 29 and eight variables, respectively. Prediction models were developed for nine variables (oxygen pulse, V˙O2, rate of CO2 production, minute ventilation, tidal volume, inspiratory capacity, end-inspiratory lung volume [in liters and as percentage of total lung capacity], and end-expiratory lung volume) using quantile regression, estimating the 5th (lower limit of normal), 50th (normal), and 95th (upper limit of normal) percentiles based on readily available participant characteristics. The two one-sided test of equivalence for paired samples evaluated the measured and 1985-predicted V˙O2 at Tvent for equivalence.Results: Reference ranges and equations were developed based on 96 participants (49% men) with a mean ± SD age of 63 ± 9 years. Mean V˙O2 at Tvent was 50% of measured V˙O2 peak; the normal range was 33% to 66%. The 1985 reference equations overpredicted V˙O2 at Tvent: mean difference in men, -0.17 L/min (95% CI, -0.25 to -0.09 L/min); mean difference in women, -0.19 L/min (95% CI, -0.27 to -0.12 L/min).Interpretation: A contemporary reference set of CPET responses at Tvent from Canadian adults 40 to 80 years of age is presented that differs from the previously recommended and often used reference set from 1985.Trial Registry: ClinicalTrials.gov; No.: NCT00920348; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Several shortcomings on cardiopulmonary exercise testing (CPET) interpretation have shed a negative light on the test as a clinically useful tool. For instance, the reader should recognize patterns of dysfunction based on clusters of variables rather than relying on rigid interpretative algorithms. Correct display of key graphical data is of foremost relevance: prolixity and redundancy should be avoided. Submaximal dyspnea ratings should be plotted as a function of work rate (WR) and ventilatory demand. Increased work of breathing and/or obesity may normalize peak oxygen uptake (V̇O2) despite a low peak WR. Among the determinants of V̇O2, only heart rate is measured during non-invasive CPET. It follows that in the absence of findings suggestive of severe impairment in O2 delivery, the boundaries between inactivity and early cardiovascular disease are blurred in individual subjects. A preserved breathing reserve should not be viewed as evidence that "the lungs" are not limiting the subject. In this context, measurements of dynamic inspiratory capacity are key to uncover abnormalities germane to exertional dyspnea. A low end-tidal partial pressure for carbon dioxide may indicate either increased "wasted" ventilation or alveolar hyperventilation; thus, direct measurements of arterial (or arterialized) PO2 might be warranted. Differentiating a chaotic breathing pattern from the normal breath-by-breath noise might be complex if the plotted data are not adequately smoothed. A sober recognition of these limitations, associated with an interpretation report free from technicalities and convoluted terminology, is crucial to enhance the credibility of CPET in the eyes of the practicing physician. [ABSTRACT FROM AUTHOR]

Background: Up-to-date normative reference sets for cardiopulmonary exercise testing (CPET) are important to aid in the accurate interpretation of CPET in clinical or research settings.Research Question: This study aimed to (1) develop and externally validate a contemporary reference set for peak CPET responses in Canadian adults identified with population-based sampling; and (2) evaluate previously recommended reference equations for predicting peak CPET responses.Study Design and Methods: Participants were healthy adults who were ≥40 years old from the Canadian Cohort Obstructive Lung Disease who completed an incremental cycle CPET. Prediction models for peak CPET responses were estimated from readily available participant characteristics (age, sex, height, body mass) with the use of quantile regression. External validation was performed with a second convenience sample of healthy adults. Peak CPET parameters that were measured and predicted in the validation cohort were assessed for equivalence (two one-sided tests of equivalence for paired-samples and level of agreement (Bland-Altman analyses). Two one-sided tests of equivalence for paired samples assessed differences between responses in the derivation cohort using previously recommended reference equations.Results: Normative reference ranges (5th-95th percentiles) for 28 peak CPET parameters and prediction models for 8 peak CPET parameters were based on 173 participants (47% male) who were 64 ± 10 years old. In the validation cohort (n = 84), peak CPET responses that were predicted with the newly generated models were equivalent to the measured values. Peak cardiac parameters predicted by the previously recommended reference equations by Jones and colleagues and Hansen and colleagues were significantly higher.Interpretation: This study provides reference ranges and prediction models for peak cardiac, ventilatory, operating lung volume, gas exchange, and symptom responses to incremental CPET and presents the most comprehensive reference set to date in Canadian adults who were ≥40 years old to be identified with population-based sampling. [ABSTRACT FROM AUTHOR]

The lung function laboratory frequently provides relevant information to the practice of pulmonology. Clinical interpretation of pulmonary function and exercise tests, however, has been complicated more recently by temporal changes in demographic characteristics (higher life expectancy), anthropometric attributes (increased obesity prevalence), and the surge of polypharmacy in a sedentary population with multiple chronic degenerative diseases. In this narrative review, we concisely discuss some key challenges to test interpretation that have been affected by these epidemiologic shifts: (a) the confounding effects of advanced age and severe obesity, (b) the contemporary controversies in the diagnosis of obstruction (including asthma and/or COPD), (c) the importance of considering the diffusing capacity of the lung for carbon monoxide (Dlco)/"accessible" alveolar volume (carbon monoxide transfer coefficient) in association with Dlco to uncover the causes of impaired gas exchange, and (d) the modern role of the pulmonary function laboratory (including cardiopulmonary exercise testing) in the investigation of undetermined dyspnea. Following a Bayesian perspective, we suggest interpretative algorithms that consider the pretest probability of abnormalities as indicated by additional clinical information. We, therefore, adopt a pragmatic approach to help the practicing pulmonologist to apply the information provided by the lung function laboratory to the care of individual patients. [ABSTRACT FROM AUTHOR]

Background: Exercise 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. Methods: This 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. Results: The 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 <0.0001). Both tests were responsive to bronchodilator treatment: there was a 19% increase in endurance time from baseline at week 6 (p = 0.0006) assessed with CWRCE, and a 20% increase in endurance time assessed with ESWT (p = 0.0013). Conclusions: Both exercise tests performed well in a multicentre clinical trial. Although the locus of symptom limitation differed between the two tests, both were reliable and responsive to bronchodilation. For future clinical trials, the choice of test should depend on the study requirements. ClinicalTrials.gov identifier: NCT01525615. The reviews of this paper are available via the supplemental material section. [ABSTRACT FROM AUTHOR]

The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (DLCO) 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 VO2 (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, DLCOCO. The higher dyspnea ratings and earlier exercise termination in low DLCO 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]

Keywords: cardiopulmonary exercise testing; inspiratory neural drive; dynamic respiratory mechanics; exertional dyspnea; physiological characterization EN cardiopulmonary exercise testing inspiratory neural drive dynamic respiratory mechanics exertional dyspnea physiological characterization 1 3 3 06/29/21 20210628 NES 210628 The value of cardiopulmonary exercise testing (CPET) is well-established as an adjunct to clinical evaluation. Unraveling the causes of unexplained dyspnea: the value of exercise testing. We hope that the pragmatic approach to CPET proposed here will help the clinician to individualize management plans by providing clear answers to a few key questions: I how severe is dyspnea and exercise intolerance in my patient i ? As resting IC diminishes over time in obstructive and restrictive disorders, critical inspiratory mechanical constraints and onset of dyspnea will occur at progressively lower V SB E sb during exercise (O'Donnell et al., [13], [14]; Neder et al., [12]). [Extracted from the article]

BACKGROUND: Single-step tests have been proposed as simple and inexpensive challenges to diagnose exercise-induced bronchoconstriction (EIB) in the pediatric population. Work performed and the resulting ventilation, however, might be substantially lower in stepping than running. This might decrease the diagnostic yield of step-based challenges. METHODS: In a cross-sectional study, 53 children with asthma with exercise-related symptoms (34 boys, age 6-18 y) underwent an incremental stepping test, a 6-min constant stepping test, and a treadmill running test on different days. RESULTS: Constant and incremental stepping tests presented with lower metabolic demands (... 1.42 ± 0.48 and 1.34 ± 0.55 L/min, respectively), ventilatory demands (... 45 ± 14 and 43 ± 16 L/min, respectively), and cardiovascular demands (160 ± 20 and 161 ± 19 beats/min, respectively) than the treadmill running test (1.65 ± 0.60 L/min, 54 ± 17 L/min, and 172 ± 7 beats/min, respectively) (P < .05). Between-test agreement in diagnosing EIB was poor (kappa 0.217- 0.361). Although EIB prevalence was higher after the treadmill running test (60%) compared to constant (53%) and incremental (47%) stepping tests, 7 subjects developed EIB only in stepping. Clinical and resting functional characteristics did not differ in discordant subjects (ie, EIB negative in a given test but positive in another) versus concordant subjects (ie, EIB negative or positive in both tests). EIB was not related to individual test ability in eliciting high to very-high ventilation (> 40% or > 60% maximum voluntary ventilation, respectively). Moreover, a negative stepping test but a positive treadmill test (and vice versa) was not associated with greater ventilatory demands. CONCLUSIONS: Lower prevalence of EIB in stepping compared to treadmill running is not related to less ventilation demand in the former modality. Although stepping might be useful as a screening EIB test due its portability and low cost, a negative test should be confirmed with a running-based test in symptomatic children. [ABSTRACT FROM AUTHOR]

Combining measurements of impaired lung mechanics (inspiratory constraints) with an index of increased respiratory stimuli to metabolic demand (poor ventilatory efficiency) might enhance the ability of cardiopulmonary exercise testing (CPET) in exposing a mechanistic role for ventilation on exertional dyspnea in COPD. In addition to the standard approach to suggest ventilatory limitation to exercise – a low breathing reserve (1−(peak ventilation (V̇E)/maximal voluntary ventilation × 100 < 20%) – we assessed the presence of critical inspiratory constraints (end-inspiratory lung volume (EILV)/total lung capacity (TLC) ≥ 0.9) and ventilatory inefficiency (V̇E/CO2 output (V̇CO2) nadir > 34) in 288 patients with mild to very severe COPD (FEV1 ranging from 18 to 121% predicted). We found that ∼50% of the patients with preserved breathing reserve developed critical inspiratory constraints. A low breathing reserve was weakly related to a lower peak O2 uptake (V̇O2) and/or a higher dyspnea burden; for instance, patients with low breathing reserve but without critical inspiratory constraints had similar dyspnea and peak V̇O2 than those with preserved breathing reserve (p > 0.05). In contrast, critical inspiratory constraints and ventilatory inefficiency were strongly associated with a negative outcome (likelihood ratio = 42.3 and 47.7, respectively; p < 0.001). A multiple logistic regression analysis revealed that only EILV/TLC ≥ 0.9 and V̇E/V̇CO2 nadir >34 predicted a severely reduced peak V̇O2 due to a high dyspnea burden (p < 0.001). Measurements of dynamic mechanical constraints and ventilatory inefficiency during incremental CPET are key to determine the impact of COPD on dyspnea and exercise tolerance across the spectrum of disease severity. [ABSTRACT FROM AUTHOR]

Smokers with minor spirometric abnormalities can experience persistent activity-related dyspnea and exercise intolerance. Additional resting tests can expose heterogeneous physiological abnormalities, but their relevance and association with clinical outcomes remain uncertain. Subjects included sixty-two smokers (≥20 pack-years), with cough and/or dyspnea and minor airway obstruction [forced expiratory volume in one-second (FEV1) ≥80% predicted and >5th percentile lower limit of normal (LLN) (i.e., z-score >−1.64) using the 2012-Global Lung Function Initiative equations]. They underwent spirometry, plethysmography, oscillometry, single-breath nitrogen washout, and symptom-limited incremental cycle exercise tests. Thirty-two age-matched nonsmoking controls were also studied. Thirty-three (53%) of smokers had chronic obstructive pulmonary disease by LLN criteria. In smokers [n= 62; age 65 ± 11 years; smoking history 43 ± 19 pack-years; post-bronchodilator FEV1z-score −0.60 ± 0.72 and FEV1/FVC z-score −1.56 ± 0.87 (mean ± SD)] versus controls, peak oxygen uptake (̇VO2) was 21 ± 7 vs. 32 ± 9 ml/kg/min, and dyspnea/̇VO2slopes were elevated (bothp< 0.0001). Smokers had evidence of peripheral airway dysfunction and maldistribution of ventilation when compared to controls. In smokers versus controls: lung diffusing capacity for carbon monoxide (DLCO) was 85 ± 22 vs. 105 ± 17% predicted, and residual volume (RV)/total lung capacity (TLC) was 36 ± 8 vs. 31 ± 6% (bothp< 0.01). The strongest correlates of peak ̇VO2were DLCO% predicted (r= 0.487,p< 0.0005) and RV/TLC% (r= −0.389,p= 0.002). DLCO% predicted was also the strongest correlate of dyspnea/̇VO2slope (r= −0.352,p= 0.005). Insmokers with mild airway obstruction, associations between resting tests of mechanics and pulmonary gas exchange and exercise performance parameters were weak, albeit consistent. Among these, DLCO showed the strongest association with important outcomes such as dyspnea and exercise intolerance measured during standardized incremental exercise tests. [ABSTRACT FROM AUTHOR]

Systolic heart failure is a common and disabling co-morbidity of chronic obstructive pulmonary disease (COPD) which may increase exercise ventilation due to heightened neural drive and/or impaired pulmonary gas exchange efficiency. The influence of heart failure on exercise ventilation, however, remains poorly characterized in COPD. In a prospective study, 98 patients with moderate to very severe COPD [41 with coexisting heart failure; ‘overlap’ (left ventricular ejection fraction < 50%)] underwent an incremental cardiopulmonary exercise test (CPET). Compared to COPD, overlap had lower peak exercise capacity despite higher FEV1. Overlap showed lower operating lung volumes, greater ventilatory inefficiency and larger decrements in end-tidal CO2(PETCO2) (P< 0.05). These results were consistent with those found in FEV1-matched patients. Larger areas under receiver operating characteristic curves to discriminate overlap from COPD were found for ventilation (E)-CO2outputCO2) intercept,E-CO2slope, peakE/CO2ratio and peak PETCO2. Multiple logistic regression analysis revealed thatCO2intercept ≤ 3.5 L/minute [odds ratios (95% CI) = 7.69 (2.61–22.65),P< 0.001] plusE-CO2slope ≥ 34 [2.18 (0.73–6.50),P= 0.14] or peakE/CO2ratio ≥ 37 [5.35 (1.96–14.59),P= 0.001] plus peak PETCO2≤ 31 mmHg [5.73 (1.42–23.15),P= 0.01] were indicative of overlapping. Heart failure increases the ventilatory response to metabolic demand in COPD. Variables reflecting excessive ventilation might prove useful to assist clinical interpretation of CPET responses in COPD patients presenting heart failure as co-morbidity. [ABSTRACT FROM PUBLISHER]

Rationale: Pulmonary rehabilitation improves dyspnea and exercise capacity in idiopathic pulmonary fibrosis (IPF); however, it is unknown whether breathing high amounts of oxygen during exercise training leads to further benefits.Objectives: Herein, we describe the design of the High Oxygen Delivery to Preserve Exercise Capacity in IPF Patients Treated with Nintedanib study (the HOPE-IPF study). The primary objective of this study is to determine the physiological and perceptual impact of breathing high levels of oxygen during exercise training in patients with IPF who are receiving antifibrotic therapy.Methods: HOPE-IPF is a two-arm double-blind multicenter randomized placebo-controlled trial of 88 patients with IPF treated with nintedanib. Patients will undergo 8 weeks of three times weekly aerobic cycle exercise training, breathing a hyperoxic gas mixture with a constant fraction of 60% inhaled oxygen, or breathing up to 40% oxygen as required to maintain an oxygen saturation level of at least 88%.Measurements and Main Results: End points will be assessed at baseline, postintervention (Week 8), and follow-up (Week 26). The primary analysis will compare the between-group baseline with post-training change in endurance time during constant work rate cycle exercise tests. Additional analyses will evaluate the impact of training with high oxygen delivery on 6-minute walk distance, dyspnea, physical activity, and quality of life.Conclusions: The HOPE-IPF study will lead to a comprehensive understanding of IPF exercise physiology, with the potential to change clinical practice by indicating the need for increased delivery of supplemental oxygen during pulmonary rehabilitation in patients with IPF. Clinical trial registered with www.clinicaltrials.gov (NCT02551068). [ABSTRACT FROM AUTHOR]

Severity of resting functional impairment only partially predicts the increased risk of death in chronic obstructive pulmonary disease (COPD). Increased ventilation during exercise is associated with markers of disease progression and poor prognosis, including emphysema extension and pulmonary vascular impairment. Whether excess exercise ventilation would add to resting lung function in predicting mortality in COPD, however, is currently unknown. After an incremental cardiopulmonary exercise test, 288 patients (forced expiratory volume in one second ranging from 18% to 148% predicted) were followed for a median (interquartile range) of 57 (47) months. Increases in the lowest (nadir) ventilation to CO2 output (VCO2) ratio determined excess exercise ventilation. Seventy-seven patients (26.7%) died during follow-up: 30/77 (38.9%) deaths were due to respiratory causes. Deceased patients were older, leaner, had a greater co-morbidity burden (Charlson Index) and reported more daily life dyspnea. Moreover, they had poorer lung function and exercise tolerance (p < 0.05). A logistic regression analysis revealed that ventilation/VCO2 nadir was the only exercise variable that added to age, body mass index, Charlson Index and resting inspiratory capacity (IC)/total lung capacity (TLC) ratio to predict all-cause and respiratory mortality (p < 0.001). Kaplan–Meier analyses showed that survival time was particularly reduced when ventilation/VCO2 nadir > 34 was associated with IC/TLC ≤ 0.34 or IC/TLC ≤ 0.31 for all-cause and respiratory mortality, respectively (p < 0.001). Excess exercise ventilation is an independent prognostic marker across the spectrum of COPD severity. Physiological abnormalities beyond traditional airway dysfunction and lung mechanics are relevant in determining the course of the disease. [ABSTRACT FROM AUTHOR]

The article discusses a study which aims to differentiate the physiologic measurements of patients with chronic bronchitis (CB) who fit the grade 1B criteria of the Global Initiative for Chronic Obstructive Lung Disease (GLOBE), and non-CB at rest and exercise. Topics discussed include the use of modified Medical Research Council dyspnea scale or COPD Assessment Test (CAT) score, and cardiopulmonary exercise test, and pulmonary and small-airway functions in both groups.

Abstract: We examined the impact of human pregnancy on breathlessness intensity at matched levels of ventilation during isoxic hyperoxic CO2 rebreathing and incremental cycle exercise tests in 21 healthy women in the third trimester (TM3) and again ∼5 months post-partum (PP). Pregnancy had no significant (P >0.05) effect on the slope or threshold of the breathlessness relationship during both exercise and rebreathing. By contrast, the slope of the breathlessness relationship was significantly higher, while the threshold of this relationship was consistently lower during rebreathing vs. exercise (both P <0.05), regardless of pregnancy status (P >0.05). As a result, breathlessness intensity was markedly higher at any given (e.g., by ∼4 Borg units at 40L/min) during rebreathing vs. exercise, regardless of pregnancy status. Inter-subject variation in breathlessness slopes during exercise was not associated with inter-subject variation in breathlessness slopes during rebreathing or with increased central chemoreflex responsiveness during pregnancy (both P >0.05). In conclusion, the intensity of perceived breathlessness for a given depends, at least in part, on the nature and source of increased central respiratory motor command output, independent of pregnancy status; and pregnancy-induced increases in activity-related breathlessness cannot be easily explained by increased central chemoreflex responsiveness. [Copyright &y& Elsevier]

Dyspnea and activity limitation are the primary symptoms of chronic obstructive pulmonary disease and progress relentlessly as the disease advances. In COPD, dyspnea is multifactorial but abnormal dynamic ventilatory mechanics are believed to be important. Dynamic lung hyperinflation occurs during exercise in the majority of flow-limited patients with chronic obstructive pulmonary disease and may have serious sensory and mechanical consequences. This proposition is supported by several studies, which have shown a close correlation between indices of dynamic lung hyperinflation and measures of both exertional dyspnea and exercise performance. The strength of this association has been further confirmed by studies that have therapeutically manipulated this dependent variable. Relief of exertional dyspnea and improved exercise endurance following bronchodilator therapy correlate well with reduced lung hyperinflation. The mechanisms by which dynamic lung hyperinflation give rise to exertional dyspnea and exercise intolerance are complex. However, recent mechanistic studies suggest that dynamic lung hyperinflation-induced volume restriction and consequent neuromechanical uncoupling of the respiratory system are key mechanisms. This review examines, in some detail, the derangements of ventilatory mechanics that are peculiar to chronic obstructive pulmonary disease and attempts to provide a mechanistic rationale for the attendant respiratory discomfort and activity limitation. [ABSTRACT FROM AUTHOR]

Activity-related dyspnea in chronic lung disease is centrally related to dynamic (dyn) inspiratory constraints to tidal volume expansion. Lack of reference values for exertional inspiratory reserve (IR) has limited the yield of cardiopulmonary exercise testing in exposing the underpinnings of this disabling symptom. One hundred fifty apparently healthy subjects (82 males) aged 40–85 underwent incremental cycle ergometry. Based on exercise inspiratory capacity (IC dyn), we generated centile-based reference values for the following metrics of IR as a function of absolute ventilation: IR dyn1 ([1-(tidal volume/IC dyn)] x 100) and IR dyn2 ([1-(end-inspiratory lung volume/total lung capacity] x 100). IR dyn1 and IR dyn2 standards were typically lower in females and older subjects (p <0.05 for sex and age versus ventilation interactions). Low IR dyn1 and IR dyn2 significantly predicted the burden of exertional dyspnea in both sexes (p <0.01). Using these sex and age-adjusted limits of reference, the clinician can adequately judge the presence and severity of abnormally low inspiratory reserves in dyspneic subjects undergoing cardiopulmonary exercise testing. • Proper interpretation of exertional inspiratory constraints requires reference values. • Females and older subjects showed higher inspiratory constraints at iso-ventilation. • Sex- and age-adjusted standards are provided for clinical use. • These norms might improve the yield of CPET in assessing exertional dyspnea. [ABSTRACT FROM AUTHOR]

Introduction: Evaluation of the intensity and quality of activity-related dyspnea is potentially useful in people with chronic obstructive pulmonary disease (COPD). The present study sought to examine associations between qualitative dyspnea descriptors, dyspnea intensity ratings, dynamic respiratory mechanics, and exercise capacity during cardiopulmonary exercise testing (CPET) in COPD and healthy controls. Methods : In this cross-sectional study, 261 patients with mild-to-very severe COPD (forced expiratory volume in 1 s, 62 +/- 25%pred) and 94 age-matched controls (forced expiratory volume in 1 s, 114 +/- 14%pred) completed an incremental cycle CPET to determine peak oxygen uptake (V[spacing dot above]O2peak). Throughout exercise, expired gases, operating lung volumes, and dyspnea intensity were assessed. At peak exercise, dyspnea quality was assessed using a modified 15-item questionnaire. Results : Logistic regression analysis revealed that among 15 dyspnea descriptors, only those alluding to the cluster "unsatisfied inspiration" were consistently associated with an increased likelihood for both critical inspiratory mechanical constraint (end-inspiratory lung volume/total lung capacity ratio >=0.9) during exercise and reduced exercise capacity (V[spacing dot above]O2peak < lower limit of normal) in COPD (odds ratio (95% confidence interval), 3.26 (1.40-7.60) and 3.04 (1.24-7.45), respectively; both, P < 0.05). Thus, patients reporting "unsatisfied inspiration" (n = 177 (68%)) had an increased relative frequency of critical inspiratory mechanical constraint and low exercise capacity compared with those who did not select this descriptor, regardless of COPD severity or peak dyspnea intensity scores. Conclusions : In patients with COPD, regardless of disease severity, reporting descriptors in the unsatisfied inspiration cluster complemented traditional assessments of dyspnea during CPET and helped identify patients with critical mechanical abnormalities germane to exercise intolerance. [ABSTRACT FROM AUTHOR]

• People with COPD had higher levels of all breathlessness sensations during exercise. • Intensity of breathlessness sensations was related to inspiratory reserve volume. • Critically low levels of inspiratory reserve volume occurred at low minute ventilation in COPD. • All groups rated work/effort of breathing higher than unsatisfied inspiration. • Only people with COPD reported moderate breathlessness-related fear and anxiety. This study compared the multidimensional breathlessness response to incremental cardiopulmonary cycle exercise testing (CPET) in people with chronic obstructive pulmonary disease (COPD; n = 14, aged 69 ± 9 years, forced expiratory volume in 1-sec = 54 ± 16 % predicted) and healthy older (OA) (n = 35, aged 68 ± 5 years) and younger (YA) (n = 19, aged 28 ± 8 years) adults. Participants performed CPET and successively rated overall breathlessness intensity, unsatisfied inspiration, breathing too shallow, work/effort of breathing, and breathlessness-related unpleasantness, fear, and anxiety using the 0−10 Borg scale. At any given percent predicted peak minute ventilation, people with COPD rated all breathlessness sensations higher than OA and YAs, who were similar. Most between group differences disappeared when examined in relation to inspiratory reserve volume, except people with COPD reported higher levels of unsatisfied inspiration and breathing too shallow (vs YA), and breathlessness-related fear and anxiety (vs OA and YAs). Multidimensional ratings of breathlessness sensations during CPET provides further insight into differences in exertional symptom perceptions among people with COPD and without COPD. [ABSTRACT FROM AUTHOR]

The functional disturbances driving "out-of-proportion" dyspnoea in patients with fibrosing interstitial lung disease (f -ILD) showing only mild restrictive abnormalities remain poorly understood. Eighteen patients (10 with idiopathic pulmonary fibrosis) showing preserved spirometry and mildly reduced total lung capacity (≥70% predicted) and 18 controls underwent an incremental cardiopulmonary exercise test with measurements of operating lung volumes and Borg dyspnoea scores. Patients' lower exercise tolerance was associated with higher ventilation (V̇ E)/carbon dioxide (V̇CO 2) compared with controls (V̇ E /V̇CO 2 nadir=35 ± 3 versus 29 ± 2; p < 0.001). Patients showed higher tidal volume/inspiratory capacity and lower inspiratory reserve volume at a given exercise intensity, reporting higher dyspnoea scores as a function of both work rate and V̇ E. Steeper dyspnoea-work rate slopes were associated with lower lung diffusing capacity, higher V̇ E /V̇CO 2 , and lower peak O 2 uptake (p < 0.05). Heightened ventilatory demands in the setting of progressively lower capacity for tidal volume expansion on exertion largely explain higher-than-expected dyspnoea in f -ILD patients with largely preserved dynamic and "static" lung volumes at rest. • The physiological abnormalities driving "out-of-proportion" dyspnea in mild f -ILD remain unclear. • Despite normal spirometry and total lung capacity typically above 70% predicted, patients showed moderate impairment in DL CO • Exertional dyspnea was related to heightened ventilatory demands and progressively lower capacity for tidal volume expansion • Exertional dyspnea and exercise intolerance were associated with lower DL CO , excess ventilation, and inspiratory constraints • These findings can causally link mild f -ILD to "out-of-proportion" dyspnoea, exposing potential therapeutic targets [ABSTRACT FROM AUTHOR]

Cardiopulmonary exercise testing (CPET) is an established method for evaluating dyspnea and ventilatory abnormalities. Ventilatory reserve is typically assessed as the ratio of peak exercise ventilation to maximal voluntary ventilation. Unfortunately, this crude assessment provides limited data on the factors that limit the normal ventilatory response to exercise. Additional measurements can provide a more comprehensive evaluation of respiratory mechanical constraints during CPET (e.g., expiratory flow limitation and operating lung volumes). These measurements are directly dependent on an accurate assessment of inspiratory capacity (IC) throughout rest and exercise. Despite the valuable insight that the IC provides, there are no established recommendations on how to perform the maneuver during exercise and how to analyze and interpret the data. Accordingly, the purpose of this manuscript is to comprehensively examine a number of methodological issues related to the measurement, analysis, and interpretation of the IC. We will also briefly discuss IC responses to exercise in health and disease and will consider how various therapeutic interventions influence the IC, particularly in patients with chronic obstructive pulmonary disease. Our main conclusion is that IC measurements are both reproducible and responsive to therapy and provide important information on the mechanisms of dyspnea and exercise limitation during CPET. [ABSTRACT FROM AUTHOR]

Abstract: We describe the case of an 86-year-old woman with advanced obstructive lung disease (forced expiratory volume in 1s/forced vital capacity ratio (FEV1/FVC)=34%) who remains capable of superior athletic performance. Detailed pulmonary function testing was performed to characterize this patient''s baseline respiratory impairment. An incremental symptom limited cycle exercise test was performed to characterize her sensory, ventilatory, cardiovascular and respiratory mechanical responses to exercise. Despite significant respiratory mechanical constraints, her peak cycle work rate and oxygen uptake were 177 and 175% predicted, respectively, and she achieved this while experiencing only moderate exertional dyspnea. She holds numerous world and national masters swim records despite her substantial objective respiratory impairment and continues to compete and set records to this day. We propose that lifelong participation in rigorous endurance training resulted in desensitization to dyspnea and has led to important cardiorespiratory adaptations that may have counterbalanced the known negative effects of obstructive lung disease on exercise performance and dyspnea. [Copyright &y& Elsevier]

The purpose of this study was to determine if altered central chemoreceptor characteristics contributed to the elevated ventilation relative to carbon dioxide production (V̇ E / V̇ CO 2) response during exercise in mild chronic obstructive pulmonary disease (COPD). Twenty-nine mild COPD and 19 healthy age-matched control participants undertook lung function testing followed by symptom-limited incremental cardiopulmonary exercise testing. On a separate day, basal (non-chemoreflex) ventilation (V̇ EB), the central chemoreflex ventilatory recruitment threshold for CO 2 (VRTCO 2), and central chemoreflex sensitivity (V̇ ES) were assessed using the modified Duffin's CO 2 rebreathing method. Resting arterialized blood gas data were also obtained. At standardized exercise intensities, absolute V̇ E and V̇ E / V̇ CO 2 were consistently elevated and the end-tidal partial pressure of CO 2 was relatively decreased in mild COPD versus controls (all p < 0.05). There were no between-group differences in resting arterialized blood gas parameters, basal V̇ E , VRTCO 2 , or V̇ ES (all p > 0.05). These data have established that excessive exercise ventilation in mild COPD is not explained by altered central chemosensitivity. [ABSTRACT FROM AUTHOR]

• Exercise limited by breathlessness was associated with distinct lung pathophysiology at peak exercise. • The qualities of exertional breathlessness was more unpleasant when it was the locus of symptom limitation to exercise. • Knowing a patient's exercise limiting symptom may allow for a more targeted and personalized approach to disease management. Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, with pulmonary and extra-pulmonary factors contributing to exercise intolerance. The primary self-reported exercise-limiting symptom may reflect the primary pathophysiological factor contributing to exercise intolerance. We compared physiological and perceptual responses at the symptom-limited peak of incremental cardiopulmonary cycle exercise testing between people with COPD reporting breathlessness (B, n = 34), leg discomfort (LD, n = 16), or a combination of B and LD (BOTH, n = 42) as their main exercise-limiting symptom(s). Despite similarly impaired health status, symptomology and peak exercise capacity, the B group had greater restrictive constraints on tidal volume expansion at end-exercise and was more likely to report unpleasant qualities of exertional breathlessness than LD and BOTH groups. In conclusion, reporting breathlessness as the primary exercise-limiting symptom indicated the presence of distinct lung pathophysiology and symptom perception during exercise in people with COPD. [ABSTRACT FROM AUTHOR]