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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., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest relative to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The causes and consequences of excess exercise ventilation (EEV) in patients with fibrosing interstitial lung disease (f-ILD) were explored. Twenty-eight adults with f-ILD and 13 controls performed an incremental cardiopulmonary exercise test. EEV was defined as ventilation-carbon dioxide output (⩒E-⩒CO 2 ) slope ≥36 L/L. Patients showed lower pulmonary function and exercise capacity compared to controls. Lower DL CO was related to higher ⩒E-⩒CO 2 slope in patients (P<0.05). 13/28 patients (46.4%) showed EEV, reporting higher dyspnea scores (P=0.033). Patients with EEV showed a higher dead space (VD)/tidal volume (VT) ratio while O 2 saturation dropped to a greater extent during exercise compared to those without EEV. Higher breathing frequency and VT/inspiratory capacity ratio were observed during exercise in the former group (P<0.05). An exaggerated ventilatory response to exercise in patients with f-ILD is associated with a blunted decrease in the wasted ventilation in the physiological dead space and greater hypoxemia, prompting higher inspiratory constraints and breathlessness., Competing Interests: Declaration of Competing Interest All authors report no relationships that could be interpreted as a conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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 O 2 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., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Dysfunctional breathing (DB) is a common, but largely underappreciated, cause of chronic dyspnoea. Under visual inspection, most subjects with DB present with larger sequential changes in ventilation (V̇E) and breathing pattern (tidal volume (VT) and breathing frequency (f)) before and/or during incremental cardiopulmonary exercise testing (CPET). Currently, however, there are no objective criteria to indicate increased ventilatory variability in these subjects., Methods: Twenty chronically dyspnoeic subjects with DB and 10 age- and sex-matched controls performed CPET on a cycle ergometer. Cut-offs to indicate increased V̇E, VT, f, and f/VT ratio variability (Δ = highest-lowest 20 s arithmetic mean) over the last resting minute ( rest ), the 2 sd min of unloaded exercise ( unload ), and the 3rd min of loaded exercise ( load ) were established by ROC curve analyses., Results: Subjects with DB presented with increased V̇E, higher ventilatory variability, higher dyspnoea burden, and lower exercise capacity compared to controls (p < 0.05). ΔV̇E load (>4.1 L/min), Δf rest (>5 breaths/min; bpm), Δf unload (>4 bpm), Δf load (>5 bpm), Δf/VT rest (>4.9 bpm/L), and Δf/VT load (>1.3 bpm/L) differentiated DB from a normal pattern (areas under the curve ranging from 0.729 to 0.845). High Δf, in particular, was associated with DB across all CPET phases., Conclusions: This study provides objective criteria to indicate increased ventilatory variability during incremental CPET in dyspnoeic subjects with DB. Large variability in breathing frequency seems particularly useful in this context, a finding that should be prospectively confirmed in larger studies., (© 2023 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Assessment of dyspnoea severity during incremental cardiopulmonary exercise testing (CPET) has long been hampered by the lack of reference ranges as a function of work rate (WR) and ventilation ( V' E ). This is particularly relevant to cycling, a testing modality which overtaxes the leg muscles leading to a heightened sensation of leg discomfort.Reference ranges based on dyspnoea percentiles (0-10 Borg scale) at standardised work rates and V' E were established in 275 apparently healthy subjects aged 20-85 years (131 men). They were compared with values recorded in a randomly selected "validation" sample (n=451; 224 men). Their usefulness in properly uncovering the severity of exertional dyspnoea were tested in 167 subjects under investigation for chronic dyspnoea ("testing sample") who terminated CPET due to leg discomfort (86 men).Iso-work rate and, to a lesser extent, iso- V' E reference ranges (5th-25th, 25th-50th, 50-75th and 75th-95th percentiles) increased as a function of age, being systematically higher in women (p<0.01). There were no significant differences in percentiles distribution between "reference" and "validation" samples (p>0.05). Submaximal dyspnoea-work rate scores fell within the 75th-95th or >95th percentiles in 108 out of 118 (91.5%) subjects of the "testing" sample who showed physiological abnormalities known to elicit exertional dyspnoea, i.e. ventilatory inefficiency and/or critical inspiratory constraints. In contrast, dyspnoea scores typically fell in the 5th-50th range in subjects without those abnormalities (p<0.001).This frame of reference might prove useful to uncover the severity of exertional dyspnoea in subjects who otherwise would be labelled as "non-dyspnoeic" while providing mechanistic insights into the genesis of this distressing symptom., Competing Interests: Conflict of interest: J.A. Neder has nothing to disclose. Conflict of interest: D.C. Berton has nothing to disclose. Conflict of interest: L.E. Nery has nothing to disclose. Conflict of interest: W.C. Tan reports grants from Canadian Respiratory Research Network, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Novartis, Canadian Institutes of Health Research, Respiratory Health Network of the Fonds de la recherche en santé du Québec, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies, during the conduct of the study. Conflict of interest: J. Bourbeau reports grants from CIHR, Canadian Respiratory Research Network (CRRN), Foundation of the MUHC and Aerocrine, personal fees for consultancy and lectures from Canadian Thoracic Society and CHEST, grants and personal fees for advisory board work and lectures from AstraZeneca, Boehringer Ingelheim, Grifols, GlaxoSmithKline, Novartis and Trudell, outside the submitted work. Conflict of interest: D.E. O'Donnell has nothing to disclose., (Copyright ©ERS 2020.)

Chronic obstructive pulmonary disease (COPD) and heart failure with reduced ejection fraction (HF) frequently coexist in the elderly. Expiratory flow limitation and lung hyperinflation due to COPD may adversely affect central hemodynamics in HF. Low lung compliance, increased alveolar-capillary membrane thickness, and abnormalities in pulmonary perfusion because of HF further deteriorates lung function in COPD. We discuss how those negative cardiopulmonary interactions create challenges in clinical interpretation of pulmonary function and cardiopulmonary exercise tests in coexisting COPD-HF. In the light of physiologic concepts, we also discuss the influence of COPD or HF on the current medical treatment of each disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Heart failure (HF) with reduced ejection fraction and chronic obstructive pulmonary disease (COPD) frequently coexist, particularly in the elderly. Given their rising prevalence and the contemporary trend to longer life expectancy, overlapping HF-COPD will become a major cause of morbidity and mortality in the next decade. Areas covered: Drawing on current clinical and physiological constructs, the consequences of negative cardiopulmonary interactions on the interpretation of pulmonary function and cardiopulmonary exercise tests in HF-COPD are discussed. Although those interactions may create challenges for the diagnosis and assessment of disease stability, they provide a valuable conceptual framework to rationalize HF-COPD treatment. The impact of COPD or HF on the pharmacological treatment of HF or COPD, respectively, is then comprehensively discussed. Authors finalize by outlining how the non-pharmacological treatment (i.e. rehabilitation and exercise reconditioning) can be tailored to the specific needs of patients with HF-COPD. Expert commentary: Randomized clinical trials testing the efficacy and safety of new medications for HF or COPD should include a sizeable fraction of patients with these coexistent pathologies. Multidisciplinary clinics involving cardiologists and respirologists trained in both diseases (with access to unified cardiorespiratory rehabilitation programs) are paramount to decrease the humanitarian and social burden of HF-COPD.

Time to exercise limitation (Tlim) in response to constant work rate (CWR) is sensitive to interventions in chronic obstructive pulmonary disease (COPD). This is particularly true when the pre-intervention test lasts between 3 and 8 min (Tlim 3'-8' ). There is, however, no simple method to select a work rate which is consistently associated with Tlim 3'-8' across the spectrum of COPD severity. We assessed 59 GOLD stages II-IV patients who initially cycled to Tlim at 75% peak. In case of short (<3 min, low-endurance) or long (>8 min, high-endurance) tests, patients exercised after 60 min at 50% or 90%, respectively (CWR 50%⇐75%⇒90% ). Critical mechanical constraints and limiting dyspnea at 75% were reached within the desired timeframe in 27 "mid-endurance" patients (46%). Increasing work rate intensity to 90% hastened the mechanical-ventilatory responses leading to Tlim 3'-8' in 23/26 (88%) "high-endurance" patients; conversely, decreasing exercise intensity to 50% slowed those responses leading to Tlim 3'-8' in 5/6 (83%) "high-endurance" patients. Repeating the tests at higher (60%) or lower (80%) intensities fail to consistently produce Tlim 3'-8' in "low-" and "high-endurance", respectively (p > 0.05). Compared to a fixed work rate at 75%, CWR 50%⇐75%⇒90% significantly decreased Tlim's coefficient of variation; consequently, the required N to detect 100 s or 33% improvement in Tlim decreased from 82 to 26 and 41 to 14, respectively. This simplified approach to individualized work rate adjustment (CWR 50%⇐75%⇒90% ) might allow greater sensitivity in evaluating interventional efficacy in improving respiratory mechanics and exercise tolerance while simultaneously reducing sample size requirements in patients with COPD.

Introduction: The application of expiratory positive airway pressure (EPAP) in patients with COPD during exercise may reduce dynamic hyperinflation, while, on the other hand, it can increase the resistive work of breathing. Therefore, we evaluated the effects of 2 intensities of EPAP during exercise on tolerance, dynamic hyperinflation, and dyspnea in subjects with moderate to very severe COPD., Methods: We performed a cross-sectional, experimental, 4-visit study. In visit 1, subjects performed symptom-limited cycling incremental cardiopulmonary exercise test (CPET). In visits 2-4, at least 48 h apart, in a randomized order, subjects performed constant CPET without EPAP, EPAP with 5 cm H 2 O (EPAP5), or EPAP with 10 cm H 2 O (EPAP10)., Results: The study included 15 non-hypoxemic subjects ranging from moderate to very severe COPD (mean FEV 1 = 35 ± 11% predicted). Increasing intensities of EPAP during constant CPET tended to cause progressive reduction in exercise tolerance ( P = .11). Of note, 10 of 15 subjects demonstrated significantly shorter average exercise duration with EPAP10 compared to the test without EPAP (-151 ± 105 s, P = .03 or -41 ± 26%). Minute ventilation increment was constrained by EPAP, secondary to a limited increase in tidal volume ( P = .01). Finally, dyspnea sensation and serial measurements of inspiratory capacity during exercise were similar when comparing the three interventions at isotime and at end-constant CPETs., Conclusions: The application of EPAP5 or EPAP10 during exercise tended to cause a progressive reduction in exercise tolerance in subjects with COPD without improvement in dyspnea or dynamic hyperinflation at equivalent exercise duration., (Copyright © 2017 by Daedalus Enterprises.)

Objective: To investigate the modulatory effects that dynamic hyperinflation (DH), defined as a reduction in inspiratory capacity (IC), has on exercise tolerance after bronchodilator in patients with COPD., Methods: An experimental, randomized study involving 30 COPD patients without severe hypoxemia. At baseline, the patients underwent clinical assessment, spirometry, and incremental cardiopulmonary exercise testing (CPET). On two subsequent visits, the patients were randomized to receive a combination of inhaled fenoterol/ipratropium or placebo. All patients then underwent spirometry and submaximal CPET at constant speed up to the limit of tolerance (Tlim). The patients who showed ΔIC(peak-rest) < 0 were considered to present with DH (DH+)., Results: In this sample, 21 patients (70%) had DH. The DH+ patients had higher airflow obstruction and lower Tlim than did the patients without DH (DH-). Despite equivalent improvement in FEV1 after bronchodilator, the DH- group showed higher ΔIC(bronchodilator-placebo) at rest in relation to the DH+ group (p < 0.05). However, this was not found in relation to ΔIC at peak exercise between DH+ and DH- groups (0.19 ± 0.17 L vs. 0.17 ± 0.15 L, p > 0.05). In addition, both groups showed similar improvements in Tlim after bronchodilator (median [interquartile range]: 22% [3-60%] vs. 10% [3-53%]; p > 0.05)., Conclusions: Improvement in TLim was associated with an increase in IC at rest after bronchodilator in HD- patients with COPD. However, even without that improvement, COPD patients can present with greater exercise tolerance after bronchodilator provided that they develop DH during exercise.

Introduction: Cardiopulmonary exercise testing (CPET) is increasingly used to evaluate the overall impact of the illness on patients with chronic obstructive pulmonary disease (COPD). While laboratory tests of exercise performance are costly, the 6-min walk test (6-MWT) can be more easily performed. Although the main outcome commonly used in this field test is the distance walked in 6 min (6-MWD), this measure does not account for differences in body weight. Previous studies showed a good correlation between the work performed during the 6-MWT with incremental cycling CPET, an exercise modality more associated with quadriceps fatigability and with lower peak oxygen consumption than incremental walking tests., Objective: Evaluate the correlation between the 6-MWD and its derivative body weight-walking distance product, an estimation of the work performed during the 6-MWT, with peak from a treadmill CPET., Methods: Thirty COPD patients [forced expiratory volume in 1 s (FEV1) = 39 ± 13%; peak predicted] performed CPET to the limit of tolerance on a treadmill and 6-MWT, 48 h apart.6-MWD and work were correlated to resting and exercise functional variables., Results: The work of walking during the 6-MWT provided greater associations with peak than observed with 6-MWD. This was the case for FEV1, forced vital capacity, inspiratory capacity, lung diffusion capacity for carbon monoxide, peak , carbon dioxide output, minute ventilation and double product (r = 0.57, r = 0.57, r = 0.73, r = 0.7, r = 0.75, r = 0.65, r = 0.51 and r = 0.4, respectively; all P < 0.05)., Conclusion: A better association was found between the work estimated from the 6-MWT and peak achieved during CPET, in this case with a treadmill, than the 6-MWD alone., (© 2012 Blackwell Publishing Ltd.)

Objective: To characterize the presence, extent, and patterns of dynamic hyperinflation (DH) during treadmill exercise testing in patients with moderate to severe COPD., Methods: This was a cross-sectional study involving 30 non-hypoxemic patients (FEV1= 43 ± 14% of predicted) who were submitted to a cardiopulmonary exercise test on a treadmill at a constant speed (70-80% of maximum speed) to the tolerance limit (Tlim). Serial inspiratory capacity (IC) maneuvers were used in order to assess DH., Results: Of the 30 patients studied, 19 (63.3%) presented with DH (DH+ group), having greater pulmonary function impairment at rest than did those without DH (DH- group). None of the variables studied correlated with exercise tolerance in the DH- group, whereas Tlim, IC, and perception of dyspnea during exercise did so correlate in the DH+ group (p < 0.05). In the DH+ group, 7 and 12 patients, respectively, presented with a progressive and a stable pattern of DH (ΔIC Tlim,2min = -0.28 ± 0.11 L vs. 0.04 ± 0.10 L; p < 0.01). Patients with a progressive pattern of DH presented with higher perception of dyspnea/Tlim rate and lower exercise tolerance than did those with a stable pattern (354 ± 118 s and 465 ± 178 s, respectively; p < 0.05)., Conclusions: The presence of DH is not a universal phenomenon during walking in COPD patients, even in those with moderate to severe airflow limitation. In the patients who presented DH, a progressive pattern of DH had a greater impact on exercise tolerance than did a stable pattern of DH.