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Cognitive and physical limitations are common in individuals with chronic lung diseases, but their interactions with physical function and activities of daily living are not well characterized. Understanding these interactions and potential contributors may provide insights on disability and enable more tailored rehabilitation strategies. This review summarizes a 2-day meeting of patient partners, clinicians, researchers, and lung associations to discuss the interplay between cognitive and physical function in people with chronic lung diseases. This report covers four areas: (1) cognitive-physical limitations in patients with chronic lung diseases; (2) cognitive assessments; (3) strategies to optimize cognition and motor control; and (4) future research directions. Cognitive and physical impairments have multiple effects on quality of life and daily function. Meeting participants acknowledged the need for a standardized cognitive assessment to complement physical assessments in patients with chronic lung diseases. Dyspnea, fatigue, and age were recognized as important contributors to cognition that can affect motor control and daily physical function. Pulmonary rehabilitation was highlighted as a multidisciplinary strategy that may improve respiratory and limb motor control through neuroplasticity and has the potential to improve physical function and quality of life. There was consensus that cognitive function and the cognitive interference of dyspnea in people with chronic lung diseases contribute to motor control impairments that can negatively affect daily function, which may be improved with pulmonary rehabilitation. The meeting generated several key research questions related to cognitive-physical interactions in individuals with chronic lung diseases. [ABSTRACT FROM AUTHOR]

Given that there are both sex-based structural differences in the respiratory system and age-associated declines in pulmonary function, the purpose of this study was to assess the effects of age and sex on the metabolic cost of breathing (V̇ o 2RM) for exercise ventilations in healthy younger and older males and females. Forty healthy participants (10 young males 24 ± 3 yr; 10 young females 24 ± 3 yr; 10 older males 63 ± 3 yr, 10 older females 63 ± 6 yr) mimicked their exercise breathing patterns (voluntary hyperpnea) in the absence of exercise across a range of exercise intensities. At peak exercise, V̇ o 2RM represented a significantly greater fraction of peak oxygen consumption (V̇ o 2peak) in young females, 12.7 ± 4.0%, compared with young males, 10.7 ± 3.0% (P = 0.027), whereas V̇ o 2RM represented 13.5 ± 2.3% of V̇ o 2peak in older females and 13.2 ± 3.3% in older males. At relative ventilations, there was a main effect of age, with older males consuming a significantly greater fraction of V̇ o 2RM (6.6 ± 1.9%) than the younger males (4.4 ± 1.3%; P = 0.012), and older females consuming a significantly greater fraction of V̇ o 2RM (6.9 ± 2.5%) than the younger females (5.1 ± 1.4%; P = 0.004) at 65% V̇ e max. Furthermore, both younger and older males had significantly better respiratory muscle efficiency than their female counterparts at peak exercise (P = 0.011; P = 0.015). Similarly, younger participants were significantly more efficient than older participants (6.5 ± 1.5% vs. 5.5 ± 2.0%; P = 0.001). Normal age-related changes in respiratory function, in addition to sex-based differences in airway anatomy, appear to influence the ventilatory responses and the cost incurred to breathe during exercise. NEW & NOTEWORTHY: Here we show that at moderate and high-intensity exercise, older individuals incur a higher cost to breathe than their younger counterparts. However, as individuals age, the sex difference in the cost of breathing narrows. Collectively, our findings suggest that the normative age-related changes in respiratory structure and function, and sex differences in airway anatomy, appear to influence the ventilatory responses to exercise and the oxygen cost to breathe. [ABSTRACT FROM AUTHOR]

In healthy adults, airway-to-lung (i.e., dysanapsis) ratio is lower and dyspnoea during exercise at a given minute ventilation (V̇E) is higher in females than in males. We investigated the relationship between dysanapsis and sex on exertional dyspnoea in healthy adults. We hypothesized that females would have a smaller airway-to-lung ratio than males and that exertional dyspnoea would be associated with airway-to-lung ratio in males and females. We analyzed data from n = 100 healthy never-smokers aged ≥40 years enrolled in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who underwent pulmonary function testing, a chest computed tomography scan, and cardiopulmonary exercise testing. The luminal area of the trachea, right main bronchus, left main bronchus, right upper lobe, bronchus intermedius, left upper lobe, and left lower lobe were 22%–37% smaller (all p < 0.001) and the airway-to-lung ratio (i.e., average large conducting airway diameter relative to total lung capacity) was lower in females than in males (0.609 ± 0.070 vs. 0.674 ± 0.082; p < 0.001). During exercise, there was a significant effect of V̇E, sex, and their interaction on dyspnoea (all p < 0.05), indicating that dyspnoea increased as a function of V̇E to a greater extent in females than in males. However, after adjusting for age and total lung capacity, there were no significant associations between airway-to-lung ratio and measures of exertional dyspnoea, regardless of sex (all r < 0.34; all p > 0.05). Our findings suggest that sex differences in airway size do not contribute to sex differences in exertional dyspnoea. [ABSTRACT FROM AUTHOR]

Background: Activation of inflammatory pathways promotes organ dysfunction in COVID-19. Currently, there are reports describing lung function abnormalities in COVID-19 survivors; however, the biological mechanisms remain unknown. The aim of this study was to analyze the association between serum biomarkers collected during and following hospitalization and pulmonary function in COVID-19 survivors. Methods: Patients recovering from severe COVID-19 were prospectively evaluated. Serum biomarkers were analyzed from admission to hospital, peak during hospitalization, and at the time of discharge. Pulmonary function was measured approximately 6 weeks after discharge. Results: 100 patients (63% male) were included (age 48 years, SD ± 14) with 85% having at least one comorbidity. Patients with a restrictive spirometry pattern (n = 46) had greater inflammatory biomarkers compared to those with normal spirometry (n = 54) including peak Neutrophil-to-Lymphocyte ratio (NLR) value [9.3 (10.1) vs. 6.5 (6.6), median (IQR), p = 0.027] and NLR at hospital discharge [4.6 (2.9) vs. 3.2 (2.9) p = 0.005] and baseline C-reactive protein value [164.0 (147.0) vs. 106.5 (139.0) mg/dL, p = 0.083). Patients with an abnormal diffusing capacity (n = 35) had increased peak NLR [8.9 (5.9) vs. 5.6 (5.7) mg/L, p = 0.029]; baseline NLR [10.0 (19.0) vs. 4.0 (3.0) pg/ml, p = 0.002] and peak Troponin-T [10.0 (20.0) vs. 5.0 (5.0) pg/ml, p = 0.011] compared to patients with normal diffusing capacity (n = 42). Multivariable linear regression analysis identified predictors of restrictive spirometry and low diffusing capacity, but only accounted for a low degree of variance in pulmonary function outcome. Conclusion: Overexpression of inflammatory biomarkers is associated with subsequent lung function abnormalities in patients recovered from severe COVID-19. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?What is the effect of lowering the normally occurring work of breathing on the electrical activity and pressure generated by the diaphragm during submaximal exercise in healthy humans?What is the main finding and its importance?Ventilatory assist during exercise elicits a proportional lowering of both the work performed by the diaphragm and diaphragm electrical activity. These findings have implications for exercise training studies using proportional assist ventilation to reduce diaphragm work in patients with cardiopulmonary disease. We hypothesized that when a proportional assist ventilator (PAV) is applied in order to reduce the pressure generated by the diaphragm, there would be a corresponding reduction in electrical activity of the diaphragm. Healthy participants (five male and four female) completed an incremental cycle exercise test to exhaustion in order to calculate workloads for subsequent trials. On the experimental day, participants performed submaximal cycling, and three levels of assisted ventilation were applied (low, medium and high). Ventilatory parameters, pulmonary pressures and EMG of the diaphragm (EMGdi) were obtained. To compare the PAV conditions with spontaneous breathing intervals, ANOVA procedures were used, and significant effects were evaluated with a Tukey–Kramer test. Significance was set at P < 0.05. The work of breathing was not different between the lowest level of unloading and spontaneous breathing (P = 0.151) but was significantly lower during medium (25%, P = 0.02) and high (36%, P < 0.001) levels of PAV. The pressure–time product of the diaphragm (PTPdi) was lower across PAV unloading conditions (P < 0.05). The EMGdi was significantly lower in medium and high PAV conditions (P = 0.035 and P < 0.001, respectively). The mean reductions of EMGdi with PAV unloading were 14, 22 and 39%, respectively. The change in EMGdi for a given lowering of PTPdi with the PAV was significantly correlated (r = 0.61, P = 0.01). Ventilatory assist during exercise elicits a reduction in the electrical activity of the diaphragm, and there is a proportional lowering of the work of breathing. Our findings have implications for exercise training studies using assisted ventilation to reduce diaphragm work in patients with cardiopulmonary disease. [ABSTRACT FROM AUTHOR]

After a bout of isolated inspiratory work, such as inspiratory pressure threshold loading (IPTL), the human diaphragm can exhibit a reversible loss in contractile function, as evidenced by a decrease in transdiaphragmatic twitch pressure (PDI,TW). Whether or not diaphragm fatigability after IPTL is affected by neural mechanisms, measured through voluntary activation of the diaphragm (D‐VA) in addition to contractile mechanisms, is unknown. It is also unknown if changes in D‐VA are similar between sexes given observed differences in diaphragm fatigability between males and females. We sought to determine whether D‐VA decreases after IPTL and whether this was different between sexes. Healthy females (n = 11) and males (n = 10) completed an IPTL task with an inspired duty cycle of 0.7 and targeting an intensity of 60% maximal transdiaphragmatic pressure until task failure. PDI,TW and D‐VA were measured using cervical magnetic stimulation of the phrenic nerves in combination with maximal inspiratory pressure maneuvers. At task failure, PDI,TW decreased to a lesser degree in females vs. males (87 ± 15 vs. 73 ± 12% baseline, respectively, p = 0.016). D‐VA decreased after IPTL but was not different between females and males (91 ± 8 vs. 88 ± 10% baseline, respectively, p = 0.432). When all participants were pooled together, the decrease in PDI,TW correlated with both the total cumulative diaphragm pressure generation (R2 = 0.43; p = 0.021) and the time to task failure (TTF, R2 = 0.40; p = 0.30) whereas the decrease in D‐VA correlated only with TTF (R2 = 0.24; p = 0.041). Our results suggest that neural mechanisms can contribute to diaphragm fatigability, and this contribution is similar between females and males following IPTL. A loss in voluntary activation after a task can be a marker of skeletal muscle fatigue. The diaphragm, the primary muscle of inspiration, exhibits a loss in voluntary activation following isolated inspiratory muscle work. When matched for total cumulative respiratory pressure generated throughout a task, males and females exhibit a similar decline in diaphragm voluntary activation. [ABSTRACT FROM AUTHOR]

Following high‐intensity, normoxic exercise there is evidence to show that healthy females, on average, exhibit less fatigue of the diaphragm relative to males. In the present study, we combined hypoxia with exercise to test the hypothesis that males and females would develop a similar degree of diaphragm fatigue following cycle exercise at the same relative exercise intensity. Healthy young participants (n = 10 male; n = 10 female) with a high aerobic capacity (120% predicted) performed two time‐to‐exhaustion (TTE; ~85% maximum) cycle tests on separate days breathing either a normoxic or hypoxic (FiO2 = 0.15) gas mixture. Fatigue of the diaphragm was assessed in response to cervical magnetic stimulation prior to, immediately post‐exercise, 10‐, 30‐, and 60‐min post‐exercise. Males and females had similar TTE durations in normoxia (males: 690 ± 181 s; females: 852 ± 401 s) and hypoxia (males: 381 ± 160 s; females: 400 ± 176 s) (p > 0.05). Cycling time was significantly shorter in hypoxia versus normoxia in both males and females (p < 0.05) and did not differ on the basis of sex (p > 0.05). Following the hypoxic TTE tests, males and females experienced a similar degree of diaphragm fatigue compared to normoxia as shown by 20%–25% reductions in transdiaphragmatic twitch pressure. This occurred despite the fact that exercise time in hypoxia was substantially shorter relative to normoxia and the cumulative diaphragm work was lower. We also observed that females did not fully recover from diaphragm fatigue in hypoxia, whereas males did (p < 0.05). Sex differences in the rate of diaphragm contractility recovery following exercise in hypoxia might relate to sex‐based differences in substrate utilization or diaphragm blood flow. [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]

The relationship between the muscle deoxygenation breakpoint (Deoxy-BP) measured with near-infrared spectrometry (NIRS), and the respiratory compensation point (RCP) has been well established. This relationship has also been reported using wearable NIRS, however not in locomotor and non-locomotor muscles simultaneously during whole-body cycling exercise. Our aim was to measure muscle oxygen saturation (SmO2) using wearable NIRS sensors, and to compare the Deoxy-BPs at each muscle with RCP during a ramp cycling exercise test. Twenty-two trained female and male cyclists completed a ramp exercise test to task intolerance on a cycling ergometer, at a ramp rate of 1 W every 2 s (30 W/min). SmO2 was recorded at the subjects' right vastus lateralis (VL) and right lateral deltoid. SmO2 and the Deoxy-BPs were assessed using a piecewise double-linear regression model. Ventilation (V̇E) and gas exchange were recorded, and RCP was determined from V̇E and gas exchange using a V-slope method and confirmed by two physiologists. The SmO2 profiles of both muscles and gas exchange responses are reported as V̇O2, power output (W), and time of occurrence (TO). SmO2 profiles at both muscles displayed a near-plateau or breakpoint response near the RCP. No differences were detected between the mean RCP and mean Deoxy-BP from either the locomotor or non-locomotor muscles; however, a high degree of individual variability was observed in the timing and order of occurrence of the specific breakpoints. These findings add insight into the relationships between ventilatory, locomotor, and non-locomotor muscle physiological breakpoints. While identifying a similar relationship between these breakpoints, individual variability was high; hence, caution is advised when using wearable NIRS to estimate RCP in an incremental ramp test. [ABSTRACT FROM AUTHOR]

Background: Individuals with COPD have increased sensitivity to traffic-related air pollution (TRAP) such as diesel exhaust (DE), but little is known about the acute effects of TRAP on exercise responses in COPD.Research Question: Does exposure before exercise to TRAP (DE titrated to 300 μg/m3 particulate matter < 2.5 μm in diameter [DE300]) show greater adverse effects on exercise endurance, exertional dyspnea, and cardiorespiratory responses to exercise in participants with mild to moderate COPD compared with former smokers with normal spirometry and healthy control participants?Study Design and Methods: In this double-blind, randomized, placebo-controlled, crossover study, 11 healthy control participants, nine former smokers without COPD, and nine former smokers with COPD were separately exposed to filtered air (FA) and DE300 for 2 h separated by a minimum of 4 weeks. Participants performed symptom-limited constant load cycling tests within 2.5 h of exposure with detailed cardiorespiratory and exertional symptom measurements.Results: A significant negative effect of TRAP on exercise endurance time was found in healthy control participants (DE300 vs FA, 10.2 ± 8.2 min vs 12.9 ± 9.5 min, respectively; P = .03), but not in former smokers without COPD (10.1 ± 6.9 min vs 12.2 ± 8.0 min, respectively; P = .57) or former smokers with COPD (9.8 ± 6.4 min vs 8.4 ± 6.6 min, respectively; P = .31). Furthermore, significant increases in inspiratory duty cycle and absolute end-expiratory and end-inspiratory lung volumes were observed, and dyspnea ratings were elevated at select submaximal measurement times only in healthy control participants.Interpretation: Contrary to our hypothesis, it was the healthy control participants, rather than the former smokers with and without COPD, who were negatively impacted by TRAP during exercise.Trial Registry: ClinicalTrials.gov; No.: NCT02236039; URL: www.Clinicaltrials: gov. [ABSTRACT FROM AUTHOR]

Background: Exercise limitation in chronic obstructive pulmonary disease (COPD) is commonly attributed to abnormal ventilatory mechanics and/or skeletal muscle function, while cardiovascular contributions remain relatively understudied. To date, the integrative exercise responses associated with different cardiopulmonary exercise limitation phenotypes in COPD have not been explored but may provide novel therapeutic utility. This study determined the ventilatory, cardiovascular, and metabolic responses to incremental exercise in patients with COPD with different exercise limitation phenotypes. Methods: Patients with COPD (n = 95, FEV1:23–113%pred) performed a pulmonary function test and incremental cardiopulmonary exercise test. Exercise limitation phenotypes were classified as: ventilatory [peak ventilation (VEpeak)/maximal ventilatory capacity (MVC) ≥ 85% or MVC-VEpeak ≤ 11 L/min, and peak heart rate (HRpeak) < 90%pred], cardiovascular (VEpeak/MVC < 85% or MVC-VEpeak > 11 L/min, and HRpeak ≥ 90%pred), or combined (VEpeak/MVC ≥ 85% or MVC-VEpeak ≤ 11 L/min, and HRpeak ≥ 90%pred). Results: FEV1 varied within phenotype: ventilatory (23–75%pred), combined (28–90%pred), and cardiovascular (68–113%pred). The cardiovascular phenotype had less static hyperinflation, a lower end-expiratory lung volume and larger tidal volume at peak exercise compared to both other phenotypes (p < 0.01 for all). The cardiovascular phenotype reached a higher VEpeak (60.8 ± 11.5 L/min vs. 45.3 ± 15.5 L/min, p = 0.002), cardiopulmonary fitness (VO2peak: 20.6 ± 4.0 ml/kg/min vs. 15.2 ± 3.3 ml/kg/min, p < 0.001), and maximum workload (103 ± 34 W vs. 72 ± 27 W, p < 0.01) vs. the ventilatory phenotype, but was similar to the combined phenotype. Conclusion: Distinct exercise limitation phenotypes were identified in COPD that were not solely dependent upon airflow limitation severity. Approximately 50% of patients reached maximal heart rate, indicating that peak cardiac output and convective O2 delivery contributed to exercise limitation. Categorizing patients with COPD phenotypically may aid in optimizing exercise prescription for rehabilitative purposes. [ABSTRACT FROM AUTHOR]

This case report characterizes the physiological responses to incremental cycling and determines the effects of 12 wk of inspiratory muscle training (IMT) on respiratory muscle strength, exercise capacity, and dyspnea in a physically active 59-yr-old female, 4 years after a left-sided extrapleural pneumonectomy (EPP). On separate days, a symptom-limited incremental exercise test and a constant work rate (CWR) test at 75% of peak work rate (WR) were completed, followed by 12 wk of IMT and another CWR test. IMT consisted of two sessions of 30 repetitions twice daily for 5 days per week. Physiological and perceptual variables were measured throughout each exercise test. The participant had a total lung capacity that was 43% predicted post-EPP. A rapid and shallow breathing pattern was adopted throughout exercise, and the ratio of minute ventilation to carbon dioxide output was elevated for a given work rate. Oxygen uptake was 71% predicted and WR was 88% predicted. Following IMT, maximal inspiratory pressure improved by 36% (-27.1 cmH2O) and endurance time by 31 s, with no observable changes in any submaximal or peak cardiorespiratory variables during exercise. The intensity and unpleasantness of dyspnea increased by 2 and 3 Borg 0-10 units, respectively, at the highest equivalent submaximal exercise time achieved on both tests. Despite having undergone a significant reduction in lung volume post-EPP, the participant achieved a relatively normal peak incremental WR, which may reflect a high level of physical conditioning. This case report also demonstrates that IMT can effectively increase respiratory muscle strength several years following EPP. [ABSTRACT FROM AUTHOR]

Ventilatory efficiency can be evaluated using the relationship between minute ventilation (V'E) and the rate of CO2 production (V'CO2). In accordance with the modified alveolar ventilation equation, this relationship is determined by changes in dead space volume (VD) and/or the arterial CO2 tension (PaCO2) equilibrium point. In this review, we summarise the physiological factors that may account for normative ageing and pregnancy induced increases in V'E/V'CO2 during exercise. Evidence suggests that age-related increases in VD and pregnancy-related decreases in the PaCO2 equilibrium point are mechanistically linked to the increased V'E/V'CO2 during exercise. Importantly, the resultant increase in V'E/V'CO2 (ratio or slope), with normal ageing or pregnancy, remains below the critical threshold for prognostic indication in cardiopulmonary disease, is not associated with increased risk of adverse health outcomes, and does not affect the respiratory system's ability to fulfil its primary role of eliminating CO2 and maintaining arterial oxygen saturation during exercise. [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]

To minimize transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for coronavirus disease (COVID-19), the U.S. Centers for Disease Control and Prevention and the World Health Organization recommend wearing face masks in public. Some have expressed concern that these may affect the cardiopulmonary system by increasing the work of breathing, altering pulmonary gas exchange and increasing dyspnea, especially during physical activity. These concerns have been derived largely from studies evaluating devices intentionally designed to severely affect respiratory mechanics and gas exchange. We review the literature on the effects of various face masks and respirators on the respiratory system during physical activity using data from several models: cloth face coverings and surgical masks, N95 respirators, industrial respirators, and applied highly resistive or high-dead space respiratory loads. Overall, the available data suggest that although dyspnea may be increased and alter perceived effort with activity, the effects on work of breathing, blood gases, and other physiological parameters imposed by face masks during physical activity are small, often too small to be detected, even during very heavy exercise. There is no current evidence to support sex-based or age-based differences in the physiological responses to exercise while wearing a face mask. Although the available data suggest that negative effects of using cloth or surgical face masks during physical activity in healthy individuals are negligible and unlikely to impact exercise tolerance significantly, for some individuals with severe cardiopulmonary disease, any added resistance and/or minor changes in blood gases may evoke considerably more dyspnea and, thus, affect exercise capacity. [ABSTRACT FROM AUTHOR]

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Most pulmonary rehabilitation (PR) programs have had to adapt due to the COVID-19 pandemic and associated restrictions. Current alternative home-based programs have limitations and require modification. In this paper, we outline a novel method to monitor home-based PR programs, which has the potential to improve PR safety and efficacy. This new method is based on a remote patient monitoring (RPM) system with connected smart devices that enables the Respiratory Therapist (RT) to have real-time access to patient data including heart rate and peripheral oxygen saturation during exercise. The RPM system also monitors daily physical activity, sedentary time, sleep quality, rescue inhaler use, and maintenance inhaler adherence, among other variables, which has the added advantage of predicting patterns consistent with symptoms that may require medical intervention. To increase privacy, data are anonymized at all levels and only the RT has access to patient information. RPM systems have the potential to give practitioners a holistic view of the participants' health status to better evaluate them during the entire PR program and to improve self-management. As this is not a formal research study, we cannot make definitive conclusions about the efficacy of the system, and further research is needed to examine safety and to compare our approach to other ways of conducting PR. [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]

New Findings: What is the central question of this study?How does sternocleidomastoid blood flow change in response to increasing ventilation and whole‐body exercise intensity?What is the main finding and its importance?Sternocleidomastoid blood flow increased with increasing ventilation. For a given ventilation, sternocleidomastoid blood flow was lower during whole‐body exercise compared to resting hyperpnoea. These findings suggest that locomotor muscle work exerts an effect on respiratory muscle blood flow that can be observed in the sternocleidomastoid. Respiratory muscle work influences the distribution of blood flow during exercise. Most studies have focused on blood flow to the locomotor musculature rather than the respiratory muscles, owing to the complex anatomical arrangement of respiratory muscles. The purpose of this study was to examine how accessory respiratory (i.e. sternocleidomastoid, and muscles in the intercostal space) muscle blood flow changes in response to locomotor muscle work. Seven men performed 5 min bouts of constant load cycling exercise trials at 30%, 60% and 90% of peak work rate in a randomized order, followed by 5 min bouts of voluntary hyperpnoea (VH) matching the ventilation achieved during each exercise (EX) trial. Blood‐flow index (BFI) of the vastus lateralis, sternocleidomastoid (SCM) and seventh intercostal space (IC) were estimated using near‐infrared spectroscopy and indocyanine green and expressed relative to resting levels. BFISCM was greater during VH compared to EX (P = 0.002) and increased with increasing exercise intensity (P = 0.036). BFISCM reached 493 ± 219% and 301 ± 215% rest during VH and EX at 90% peak work rate, respectively. BFIIC increased to 242 ± 178% and 210 ± 117% rest at 30% peak work rate during VH and EX, respectively. No statistically significant differences in BFIIC were observed with increased work rate during VH or EX (both P > 0.05). Moreover, there was no observed difference in BFIIC between conditions (P > 0.05). BFISCM was lower for a given minute ventilation during EX compared to VH, suggesting that accessory respiratory muscle blood flow is influenced by whole‐body exercise. [ABSTRACT FROM AUTHOR]

Purpose: (1) To determine whether healthy humans can distinguish between the intensity and unpleasantness of exertional dyspnoea; (2) to evaluate the reliability of qualitative dyspnoea descriptors during exercise; and (3) to assess the reliability of the Multidimensional Dyspnoea Profile (MDP) Methods: Forty-four healthy participants (24M:20F, 25 ± 5 years) completed maximal incremental cycling tests on three visits. During visit 1, participants rated the intensity and unpleasantness of dyspnoea simultaneously throughout exercise using the modified 0–10 category-ratio Borg scale. On visits 2 and 3, participants rated either the intensity or unpleasantness of dyspnoea alone at the same measurement times as visit 1. On all visits, participants selected qualitative descriptors throughout all exercise intensities from a list of 4, selected relevant qualitative descriptors from a list of 15 at peak exercise, and completed the MDP. Results: Participants rated their dyspnoea intensity significantly higher for a given minute ventilation ( V ˙ E ) compared to dyspnoea unpleasantness (dyspnoea- V ˙ E slope: 0.08 ± 0.02 vs. 0.07 ± 0.03 Borg 0–10/L min−1, p < 0.001) during visit 1. The onset of intensity ratings occurred at a significantly lower work rate compared to unpleasantness ratings measured on the same exercise test (52 ± 41 vs. 91 ± 53 watts, p < 0.001). Dyspnoea intensity and unpleasantness remained significantly different for a given ventilation even when measured independently on separate exercise tests (p < 0.05). There was good-to-excellent reliability (ICC > 0.60) for the use of qualitative dyspnoea descriptors and the MDP to measure dyspnoea at peak exercise. Conclusion: Exercise-induced dyspnoea in healthy adults can differ in the sensory and affective dimensions, and can be measured reliably using qualitative descriptors and the MDP. [ABSTRACT FROM AUTHOR]

Key points: Diaphragm fatigue may increase the intensity (sensory dimension) and unpleasantness (affective dimension) of dyspnoea, which may partially explain why diaphragm fatigue negatively affects exercise performance.We hypothesized that diaphragm fatigue would negatively affect exercise performance via increases in both the intensity and unpleasantness of dyspnoea, and that the increase in dyspnoea would be mechanistically linked to an increase in diaphragmatic EMG (EMGdi), a surrogate measure of neural respiratory drive.Fatiguing the diaphragm prior to exercise reduced cycling performance and increased both the intensity and unpleasantness of dyspnoea. The change in submaximal dyspnoea unpleasantness was significantly correlated with the change in cycling performance.Pre‐fatigue of the diaphragm did not increase EMGdi during exercise and is therefore unrelated to the increase in either the sensory or affective dimension of exertional dyspnoea. The purpose of this study was to examine the effect of diaphragm fatigue on the multidimensional components of dyspnoea and diaphragm electromyography (EMGdi) during cycling. Sixteen healthy males (age = 27 ± 5 yr, V̇O2max = 45.8 ± 9.8 ml kg−1 min−1) completed two high‐intensity, time‐to‐exhaustion cycling tests in randomized order: (i) inspiratory pressure threshold loading (PTL) prior to exercise to induce diaphragm fatigue (pre‐DF) and (ii) no PTL (control). Diaphragm fatigue after PTL was confirmed via cervical magnetic stimulation of the phrenic nerves. Dyspnoea intensity and unpleasantness were measured throughout exercise with the 0–10 category‐ratio Borg scale and following exercise using the Multidimensional Dyspnoea Profile (MDP). EMGdi was continuously recorded via a multipair oesophageal electrode catheter. Time‐to‐exhaustion decreased with pre‐DF vs. control (9.0 ± 5.5 vs. 10.7 ± 7.5 min, P = 0.023). Pre‐DF increased dyspnoea intensity ratings by 0.6 ± 1.0 Borg 0–10 units at the highest equivalent submaximal exercise time (HESET) a participant could achieve in both conditions (P = 0.020). Dyspnoea unpleasantness ratings increased with pre‐DF by 0.5 ± 1.0, 0.7 ± 1.2 and 0.9 ± 1.4 (all P < 0.05) Borg 0–10 units during the 2nd, 3rd and 4th minutes of exercise, respectively. There was a significant correlation between the change in breathing unpleasantness ratings at HESET and the change in time‐to‐exhaustion (r = 0.66, P = 0.006). The immediate perception domain, a combination of peak unpleasantness and specific dyspnoea descriptor intensity ratings, was the only component of the MDP that was significantly increased with pre‐DF (4.3 ± 1.9 vs. 3.6 ± 1.8, P = 0.04). There were no significant differences in EMGdi. In conclusion, diaphragm fatigue has negative effects on multiple domains of dyspnoea, which may partially explain why exercise performance decreases with it. Key points: Diaphragm fatigue may increase the intensity (sensory dimension) and unpleasantness (affective dimension) of dyspnoea, which may partially explain why diaphragm fatigue negatively affects exercise performance.We hypothesized that diaphragm fatigue would negatively affect exercise performance via increases in both the intensity and unpleasantness of dyspnoea, and that the increase in dyspnoea would be mechanistically linked to an increase in diaphragmatic EMG (EMGdi), a surrogate measure of neural respiratory drive.Fatiguing the diaphragm prior to exercise reduced cycling performance and increased both the intensity and unpleasantness of dyspnoea. The change in submaximal dyspnoea unpleasantness was significantly correlated with the change in cycling performance.Pre‐fatigue of the diaphragm did not increase EMGdi during exercise and is therefore unrelated to the increase in either the sensory or affective dimension of exertional dyspnoea. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine scalene (SA) and sternocleidomastoid (SM) activation during normoxic (norm‐ITL; FIO2 = 21%) and hypoxic (hyp‐ITL; FIO2 = 15%) incremental inspiratory threshold loading (ITL). Thirteen healthy participants (33 ± 4 years, 9 female) performed two ITL tests breathing randomly assigned gas mixtures through an inspiratory loading device where the load was increased every two minutes until task failure. SA and SM root mean square (RMS) electromyography (EMG) were calculated and expressed as a percentage of maximum (RMS%max) to reflect muscle activation intensity. Myoelectric manifestations of fatigue were characterized as decreased SA or SM EMG median frequency during maximum inspiratory pressure maneuvers before and after ITL. Dyspnea was recorded at baseline and task failure. Ventilatory parameters and mouth pressure (Pm) were recorded throughout the ITL. SA,RMS%max and SM,RMS%max increased in association with ITL load (p ≤.01 for both). SA,RMS%max was similar between norm‐ITL and hyp‐ITL (p =.17), whereas SM,RMS%max was greater during the latter (p =.001). Neither SA nor SM had a decrease in EMG median frequency after ITL (p =.75 and 0.69 respectively). Pm increased in association with ITL load (p <.001) and tended to be higher during hyp‐ITL compared to norm‐ITL (p =.05). Dyspnea was similar during both conditions (p >.05). There was a trend for higher tidal volumes during hyp‐ITL compared to norm‐ITL (p =.10). Minute ventilation was similar between both conditions (p =.23). RMS,%max of the SA and SM increased linearly with increasing ITL. The presence of hypoxia only increased SM activation. Neither SA nor SM presented myoelectric manifestations of fatigue during both conditions. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) is a heterogeneous group of conditions characterized by fibrosis and/or inflammation of the lung parenchyma. The pathogenesis of ILD consistently results in exertional dyspnea and exercise intolerance. Cardiopulmonary exercise testing (CPET) provides important information concerning the pathophysiology of ILD that can help inform patient management. Despite the purported benefits of CPET, its clinical utility in ILD is not well defined; however, there is a growing body of evidence that provides insight into the potential value of CPET in ILD. Characteristic responses to CPET in patients with ILD include exercise-induced arterial hypoxemia, an exaggerated ventilatory response, a rapid and shallow breathing pattern, critically low inspiratory reserve volume, and elevated sensations of dyspnea and leg discomfort. CPET is used in ILD to determine cause(s) of symptoms such as exertional dyspnea, evaluate functional capacity, inform exercise prescription, and determine the effects of pharmacological and non-pharmacological interventions on exercise capacity and exertional symptoms. However, preliminary evidence suggests that CPET in ILD may also provide valuable prognostic information and can be used to ascertain the degree of exercise-induced pulmonary hypertension. Despite these recent advances, additional research is required to confirm the utility of CPET in patients with ILD. This brief review outlines the clinical utility of CPET in patients with ILD. Typical patterns of response are described and practical issues concerning CPET interpretation in ILD are addressed. Additionally, important unanswered questions relating to the clinical utility of CPET in the assessment, prognostication, and management of patients with ILD are identified. [ABSTRACT FROM AUTHOR]

Rationale: Lumacaftor/ivacaftor (LUM/IVA) modestly improves lung function following 1 month of treatment but it is unknown if this translates into improvements in exercise endurance and exertional symptoms.Methods: Adult CF participants completed a symptom-limited constant load cycling test with simultaneous assessments of dyspnea and leg discomfort ratings pre- and 1 month post-initiation of LUM/IVA.Results: Endurance time, exertional dyspnea and leg discomfort ratings at submaximal exercise did not change significantly. There was a significant inverse correlation between changes in leg discomfort and endurance time (r = - 0.88; p = 0.009) following 1-month of LUM/IVA.Conclusions: Overall, 1-month of LUM/IVA did not increase endurance time or modify exertional dyspnea or leg discomfort ratings. However, individuals who experienced a reduction in leg discomfort following LUM/IVA had an improvement in endurance time. Future studies with a larger sample size are needed to verify these findings and to assess the long-term effects of LUM/IVA on exercise outcomes.Trial Registration: ClinicalTrials.gov Identifier: NCT02821130. Registered July 1, 2016. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?What is the effect of age and sex on the resistive and viscoelastic components of work of breathing (Wb) during exercise?What is the main finding and its importance?The resistive and viscoelastic components of Wb were higher in older adults, regardless of sex. The resistive, but not viscoelastic, component of Wb was higher in females than in males, regardless of age. These findings contribute to improving our understanding of the effects of ageing and sex on the mechanical ventilatory response to exercise. Healthy ageing and biological sex each affect the work of breathing (Wb) for a given minute ventilation (V̇E). Age‐related structural changes to the respiratory system lead to an increase in both the resistive and viscoelastic components of Wb; however, it is unclear whether healthy ageing differentially alters the mechanics of breathing in males and females. We analysed data from 22 older (60–80 years, n = 12 females) and 22 younger (20–30 years, n = 11 females) males and females that underwent an incremental cycle exercise test to exhaustion. V̇E and Wb were assessed at rest and throughout exercise. Wb–V̇E data for each participant were fitted to a non‐linear equation (i.e. Wb = aV̇E3 + bV̇E2) that partitions Wb into resistive (i.e. aV̇E3) and viscoelastic (i.e. bV̇E2) components. We then modelled the effects of healthy ageing and biological sex on each component of Wb. Overall, the model fit was excellent (r2: 0.99 ± 0.01). There was a significant main effect of age and sex on the resistive component of Wb (both P < 0.05), and a significant main effect of age (P < 0.001), but not sex (P = 0.309), on the viscoelastic component of Wb. No significant interactions between age and sex on aV̇E3 or bV̇E2 were noted (both P > 0.05). Our findings indicate that during exercise: (i) the higher total Wb in females relative to males is due to a higher resistive, but not viscoelastic, component of Wb, and (ii) regardless of sex, the higher Wb in older adults relative to younger adults is due to higher resistive and viscoelastic components of Wb. [ABSTRACT FROM AUTHOR]

Adult survivors of very preterm (≤32 wk gestational age) birth without (PRE) and with bronchopulmonary dysplasia (BPD) have variable degrees of airflow obstruction at rest. Assessment of the shape of the maximal expiratory flow-volume (MEFV) curve in PRE and BPD may provide information concerning their unique pattern of airflow obstruction. The purposes of the present study were to 1) quantitatively assess the shape of the MEFV curve in PRE, BPD, and healthy adults born at full-term (CON), 2) identify where along the MEFV curve differences in shape existed between groups, and 3) determine the association between an index of MEFV curve shape and characteristics of preterm birth (i.e., gestational age, mass at birth, duration of oxygen therapy) in PRE and BPD. To do so, we calculated the average slope ratio (SR) throughout the effort-independent portion of the MEFV curve and at increments of 5% of forced vital capacity (FVC) between 20 and 80% of FVC in PRE (n = 19), BPD (n = 25), and CON (n = 20). We found that average SR was significantly higher in PRE (1.34 ± 0.35) and BPD (1.33 ± 0.45) compared with CON (1.03 ± 0.22; both P < 0.05) but similar between PRE and BPD (P = 0.99). Differences in SR between groups occurred early in expiration (i.e., 20–30% of FVC). There was no association between SR and characteristics of preterm birth in PRE and BPD groups (all P > 0.05). The mechanism(s) of increased SR during early expiration in PRE/BPD relative to CON is unknown but may be due to differences in the structural and mechanical properties of the airways. [ABSTRACT FROM AUTHOR]

Purpose: The impact of psychological deficits and pain on physical activity has not been adequately studied in patients with fibrotic interstitial lung disease (ILD). We aimed to determine the association of depression, anxiety, sleep quality, and pain with physical activity in fibrotic ILD. Methods: Waist ActiGraph activity monitors were worn for seven consecutive days to track step counts and moderate-to-vigorous physical activity (MVPA) minutes at baseline and 6-month follow-up. Psychological deficits and pain were assessed using the Hospital Anxiety and Depression Scale, the Pittsburgh Sleep Quality Index, and the Brief Pain Inventory. Multivariable linear regression was used to determine if each deficit independently predicted physical activity when adjusted for potential confounders. Results: A total of 111 patients were recruited, with 91 of these patients completing the 6-month follow-up. Median step count and MVPA minutes were 3853 steps/day (interquartile range 2236–6805) and 87 (17–225) min/week at baseline, respectively, with no significant changes at follow-up. Borderline or abnormal depression and anxiety scores were present in 19% and 22% of patients, respectively. Poor sleep quality and moderate-to-severe pain were present in 61% and 9% of patients. Higher depression scores were associated with fewer baseline and follow-up step counts and lower MVPA minutes at follow-up on unadjusted analysis; higher pain severity scores were associated with fewer baseline step count. Pain severity remained an independent predictor of reduced step count after adjusting for patient's age, smoking status, ILD severity, and weather variables. Conclusions: Pain severity may be a potentially modifiable determinant of physical activity in patients with fibrotic ILD. [ABSTRACT FROM AUTHOR]

Background: Toe-in and toe-out walking are 2 strategies that have been shown to be effective in reducing the knee adduction moment in people with knee osteoarthritis. However, despite a positive biomechanical impact on the knee, altering foot rotation may impart unintended forces or joint positions on the ankle that could impact joint health. The kinematic and kinetic changes at the ankle during toe-in or toe-out walking have yet to be examined.Objective: To examine ankle/rearfoot biomechanics during toe-in and toe-out walking in those with knee osteoarthritis.Design: Single-session repeated measures design to compare ankle biomechanics during walking with 4 different foot rotations.Setting: University motion analysis laboratory.Participants: A convenience sample (N = 15) of males and females with a diagnosis of medial knee osteoarthritis confirmed by radiographs.Methods: Participants walked in 4 conditions guided by real-time biofeedback: (1) toe-in (+10°), (2) zero rotation (0°), (3) toe-out (-10°), and (4) toe-out (-20°). Ankle and rearfoot kinematics and kinetics were examined during barefoot over-ground walking.Main Outcome Measures: Ankle joint angles, moments, moment impulses, and foot rotation.Results: Overall, toe-in compared to toe-out walking decreased (P = .03) peak rearfoot eversion (toe-in = -1.6°; 10° toe-out = -3.7°; 20° toe-out = -4.1°). Toe-in compared to toe-out walking also increased rearfoot inversion at initial contact (7.4° vs 3.1° at 10° toe-out and 1.9° at 20° toe-out; P < .001) and frontal plane rearfoot angle excursion (9.0° vs 6.8° at 10° toe-out and 6.0° at 20° toe-out; P < .006). Toe-in compared to all other conditions increased peak external ankle inversion moments (0.04 Nm/kg vs 0.02 Nm/kg at 0°, 0.02 Nm/kg at 10° toe-out, and 0.01 Nm/kg at 20° toe-out; P < .003).Conclusions: Toe-in and toe-out walking require different ankle/rearfoot biomechanics, though no differences in discomfort were observed. Longer-term studies are required to properly assess these relationships in knee osteoarthritis populations.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

Key points: The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex‐differences in respiratory system morphology.During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea.Using a single‐blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate‐intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults.When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. We aimed to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. Eighteen healthy subjects (aged 60–80 years; nine men and nine women) completed two days of testing. On day 1, subjects were assessed for pulmonary function and performed a maximal incremental cycle exercise test. On day 2, subjects performed three 6‐min bouts of cycling at ventilatory threshold, in a single‐blind randomized manner, while breathing: (i) normoxic helium‐oxygen (HEL) to reduce the work of breathing (Wb) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH2O L−1 s−1 to increase Wb; and (iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (category‐ratio 10 Borg scale) were monitored throughout exercise. During the HEL condition, there was a significant decrease in Wb (men: –21 ± 6%, women: –17 ± 10%) relative to CON (both P < 0.01). Moreover, if EFL was present during CON (four men and five women), it was alleviated during HEL. Conversely, during the RES condition, Wb (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on Wb (P = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, P < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, the intensity of dyspnoea was unaffected, independent of sex (P = 0.46). When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. Key points: The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex‐differences in respiratory system morphology.During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea.Using a single‐blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate‐intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults.When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. [ABSTRACT FROM AUTHOR]

Many adults with single-ventricle congenital heart disease who have undergone a Fontan procedure have abnormal pulmonary function resembling restrictive lung disease. Whether this contributes to ventilatory limitations and increased dyspnea has not been comprehensively studied. We recruited 17 Fontan participants and 17 healthy age- and sex-matched sedentary controls. All participants underwent complete pulmonary function testing followed by a symptom-limited incremental cardiopulmonary cycle exercise test with detailed assessments of dyspnea and operating lung volumes. Fontan participants and controls were well matched for age, sex, body mass index, height, and self-reported physical activity levels (all P > 0.05), although Fontan participants had markedly reduced cardiorespiratory fitness and peak work rates ( P < 0.001). Fontan participants had lower values for most pulmonary function measurements relative to controls with 65% of Fontan participants showing evidence of a restrictive ventilatory defect. Relative to controls, Fontan participants had significantly higher breathing frequency, end-inspiratory lung volume (% total lung capacity), ventilatory inefficiency (high ventilatory equivalent for CO2), and dyspnea intensity ratings at standardized absolute submaximal work rates. There were no between-group differences in qualitative descriptors of dyspnea. The restrictive ventilatory defect in Fontan participants likely contributes to their increased breathing frequency and end-inspiratory lung volume during exercise. This abnormal ventilatory response coupled with greater ventilatory inefficiency may explain the increased dyspnea intensity ratings in those with a Fontan circulation. Interventions that enhance the ventilatory response to exercise in Fontan patients may help optimize exercise rehabilitation interventions, resulting in improved exercise tolerance and exertional symptoms. NEW & NOTEWORTHY This is the first study to comprehensively characterize both ventilatory and sensory responses to exercise in adults that have undergone the Fontan procedure. The majority of Fontan participants had a restrictive ventilatory defect. Compared with well-matched controls, Fontan participants had increased breathing frequency, end-inspiratory lung volume, and ventilatory inefficiency. These abnormal ventilatory responses likely form the mechanistic basis for the increased dyspnea intensity ratings observed in our Fontan participants during exercise. [ABSTRACT FROM AUTHOR]

Rationale: The optimal method of physical activity measurement has not been determined in patients with fibrotic interstitial lung disease (ILD).Objectives: To assess the validity, internal consistency, and responsiveness of the International Physical Activity Questionnaire long form (IPAQ-LF) and to estimate the minimal important difference (MID) for moderate to vigorous physical activity (MVPA) in patients with fibrotic ILD.Methods: This two-center prospective cohort study included a convenience sample of 111 outpatients with fibrotic ILD who wore waist and wrist ActiGraph accelerometers for 7 consecutive days, followed by self-administration of the IPAQ-LF. Both measurements were performed at baseline and 6-month follow-up. Spearman rank correlations were used to evaluate the IPAQ-LF validity in comparison to activity monitor data, lung function, step count, and quality of life. The internal consistency of the IPAQ-LF was determined using Cronbach's α. Self-reported changes in IPAQ-LF parameters were compared among tertiles of change measured by the waist activity monitor to assess the responsiveness of the IPAQ-LF after 6 months. Anchor- and distribution-based methods were used to estimate the MID for MVPA.Results: Self-reported MVPA minutes, activity-related energy expenditure, sedentary time, and inactive time of the IPAQ-LF generally showed moderate to strong correlations with corresponding waist activity monitor data, step count, lung function, and quality of life. The Cronbach's α of the IPAQ-LF was 0.78. The IPAQ-LF was responsive at detecting increases in weekly MVPA and energy expenditure. The MIDs for MVPA were 8 to 26 and 13 to 58 min/wk using the anchor-based method for waist activity monitor and IPAQ-LF data, respectively. The distribution-based MID estimate for MVPA was 104 to 242 min/wk.Conclusions: The IPAQ-LF has acceptable validity and internal consistency for measuring daily physical activity in patients with fibrotic ILD. The IPAQ-LF was responsive at detecting increases in physical activity but limited in its ability to detect declines or changes in inactivity. Using an anchor-based approach, the MID for MVPA measured by a waist activity monitor is approximately 26 min/wk. [ABSTRACT FROM AUTHOR]

Women are more resistant to diaphragmatic fatigue (DF) and experience an attenuated inspiratory muscle metaboreflex relative to men. The effects of such sex-based differences on whole body exercise tolerance are yet to be examined. It was hypothesized that DF induced prior to exercise would cause less of a reduction in subsequent exercise time in women compared to men. Healthy men ( n = 9, age = 24 ± 3 yr) and women ( n = 9, age = 24 ± 3 yr) completed a maximal incremental cycle test on day 1. On day 2, subjects performed isocapnic inspiratory pressure-threshold loading (PTL) to task failure followed by a constant load submaximal time-to-exhaustion (TTE) exercise test at 85% of the predetermined peak work rate. On day 3, subjects performed the same exercise test without prior induced DF. Days 2 and 3 were randomized and counterbalanced. Magnetic stimulation of the phrenic nerve roots was used to nonvolitionally assess DF by measurement of transdiaphragmatic twitch pressure ( Pdi,tw). A similar degree of DF was produced in both sexes following PTL [ Pdi,tw (% change from baseline): M = -24.6 ± 7.8%, W = -23.1 ± 5.4%; P = 0.54)]. There was a significant reduction in TTE with prior induced DF compared with the control condition in both men (10.9 ± 3.5 min vs. 13.0 ± 3.2 min, P = 0.05) and women (10.1 ± 2.4 min vs. 12.2 ± 3.3 min, P = 0.03) that did not differ in magnitude between the sexes (M = -15.8 ± 19.5%, W = -14.5 ± 19.2%, P = 0.89). In conclusion, DF negatively and equally impairs exercise tolerance independent of sex. NEW & NOTEWORTHY Women are more resistant to diaphragmatic fatigue (DF) relative to men. The effect of DF on exercise tolerance is currently being debated. Our findings show that DF negatively and equally affects exercise tolerance in healthy men and women. Mechanisms beyond the inspiratory muscle metaboreflex (e.g., dyspnea, central fatigue, breathing pattern) may explain the absence of a sex-based difference. [ABSTRACT FROM AUTHOR]

Purpose: To non-invasively examine the effect of acute hypoxia and inspiratory threshold loading (ITL) on inspiratory muscles [sternocleidomastoid (SCM), scalene (SA) and parasternal (PS)] oxygenation in healthy adults using near-infrared spectroscopy (NIRS).Methods: Twenty healthy adults (12 M/8 F) were randomly assigned to perform two ITL tests while breathing a normoxic or hypoxic (FIO2 = 15 %) gas mixture. NIRS devices were placed over the SCM, PS, SA, and a control muscle, tibialis anterior (TA), to monitor oxygenated (O2Hb), deoxygenated (HHb), total hemoglobin (tHb) and tissue saturation index (TSI). With the nose occluded, subjects breathed normally for 4 min through a mouthpiece that was connected to a weighted threshold loading device. ITL began by adding a 100-g weight to the ITL device. Then, every 2 min 50-g was added until task failure. Vital signs, ECG and ventilatory measures were monitored throughout the protocol.Result: Participants were 31 ± 12 year and had normal spirometry. At task failure, the maximum load and ventilatory parameters did not differ between the hypoxic and normoxic ITL. At hypoxic ITL task failure, SpO2 was significantly lower, and ∆HHb increased more so in SA, SCM and PS than normoxic values. SCM ∆TSI decreased more so during hypoxic compared to normoxic ITL. ∆tHb in the inspiratory muscles (SCM, PS and SA) increased significantly compared to the decrease in TA during both hypoxic and normoxic ITL.Conclusion: The SCM, an accessory inspiratory muscle was the most vulnerable to deoxygenation during incremental loading and this response was accentuated by acute hypoxia. [ABSTRACT FROM AUTHOR]

Key points: Diaphragmatic fatigue (DF) elicits a sympathetically mediated metaboreflex resulting in increased heart rate, blood pressure and limb vascular resistance. Women may be more resistant to DF compared to men, and therefore it was hypothesised that women would experience an attenuated inspiratory muscle metaboreflex during inspiratory pressure‐threshold loading (PTL) performed to task failure. At the time of PTL task failure, the severity of DF was not different between sexes; however, inspiratory muscle endurance time was significantly longer in women than in men. For a given cumulative diaphragmatic force output, the severity of DF was less in women than in men. Women exhibited a blunted cardiovascular response to inspiratory resistance (i.e. metaboreflex) that may have implications for exercise tolerance. Abstract: Diaphragmatic fatigue (DF) elicits reflexive increases in sympathetic vasomotor outflow (i.e. metaboreflex). There is some evidence suggesting women may be more resistant to DF compared to men, and therefore may experience an attenuated inspiratory muscle metaboreflex. To this end, we sought to examine the cardiovascular response to inspiratory resistance in healthy young men (n = 9, age = 24 ± 3 years) and women (n = 9, age = 24 ± 3 years). Subjects performed isocapnic inspiratory pressure‐threshold loading (PTL, 60% maximal inspiratory mouth pressure) to task failure. Diaphragmatic fatigue was assessed by measuring transdiaphragmatic twitch pressure (Pdi,tw) using cervical magnetic stimulation. Heart rate (HR) and mean arterial pressure (MAP) were measured beat‐by‐beat throughout PTL via photoplethysmography, and low‐frequency systolic pressure (LFSBP; a surrogate for sympathetic vasomotor tone) calculated from arterial waveforms using power spectrum analysis. At PTL task failure, the degree of DF was similar between sexes (∼23% reduction in Pdi,tw; P = 0.33). However, time to task failure was significantly longer in women than in men (27 ± 11 vs. 16 ± 11 min, respectively; P = 0.02). Women exhibited less of an increase in HR (13 ± 8 vs. 19 ± 12 bpm; P = 0.02) and MAP (10 ± 8 vs. 14 ± 9 mmHg; P = 0.01), and significantly lower LFSBP (23 ± 11 vs. 34 ± 8 mmHg2; P = 0.04) during PTL compared to men. An attenuation of the inspiratory muscle metaboreflex may influence limb and respiratory muscle haemodynamics with implications for exercise performance. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background and objective: Despite its clinical and prognostic significance, few studies have evaluated the severity of exertional oxygen desaturation in fibrotic interstitial lung disease (ILD). Our objectives were to identify clinical and physiological variables that predict the extent of exertional oxygen desaturation in fibrotic ILD and to quantify the severity of desaturation compared to chronic obstructive pulmonary disease (COPD). Methods: This retrospective study compared the results of 6‐min walk test (6MWT) performed while breathing room air in fibrotic ILD patients and COPD patients eligible for pulmonary rehabilitation. Outcomes included the oxygen saturation (SpO2) nadir and the change in SpO2 from rest during a 6MWT. Predictor variables were identified on unadjusted analysis, followed by multivariate analysis to identify independent predictors of desaturation. Results: The study included 134 patients with fibrotic ILD and 274 patients with COPD. The ILD and COPD cohorts had similar age, sex, frequency of major comorbidities, walk distance, baseline SpO2 and baseline Borg dyspnoea scores. DLCO was the strongest predictor of desaturation in both cohorts. Compared to patients with COPD, ILD patients had significantly lower SpO2 nadir values (88.1 ± 6.4 vs 91.0 ± 4.6) and greater decrease in SpO2 from baseline (7.4 ± 5.2 vs 4.5 ± 3.7) after adjusting for demographic features and pulmonary physiology (P < 0.0005), with greater between‐group differences at lower DLCO values. Conclusion: Patients with fibrotic ILD have greater oxygen desaturation during 6MWT compared to patients with COPD when adjusting for demographic features and pulmonary physiology. These findings suggest the need for disease‐specific studies to evaluate the potential utility of ambulatory oxygen in fibrotic ILD. [ABSTRACT FROM AUTHOR]

We examined the effects of age, sex, and their interaction on mechanical ventilatory constraint and dyspnea during exercise in 22 older (age = 68 ± 1 yr; n = 12 women) and 22 younger (age = 25 ± 1 y, n = 11 women) subjects. During submaximal exercise, older subjects had higher end-inspiratory (EILV) and end-expiratory (EELV) lung volumes than younger subjects (both P < 0.05). During maximal exercise, older subjects had similar EILV ( P > 0.05) but higher EELV than younger subjects ( P < 0.05). No sex differences in EILV or EELV were observed. We noted that women had a higher work of breathing (Wb) for a given minute ventilation (V̇e) ≥65 l/min than men ( P < 0.05) and older subjects had a higher Wb for a given V̇e ≥60 l/min ( P < 0.05). No sex or age differences in Wb were present at any submaximal relative V̇e. At absolute exercise intensities, older women experienced expiratory flow limitation (EFL) more frequently than older men ( P < 0.05), and older subjects were more likely to experience EFL than younger subjects ( P < 0.05). At relative exercise intensities, women and older individuals experienced EFL more frequently than men and younger individuals, respectively (both P < 0.05). There were significant effects of age, sex, and their interaction on dyspnea intensity during exercise at absolute, but not relative, intensities (all P < 0.05). Across subjects, dyspnea at 80 W was significantly correlated with indexes of mechanical ventilatory constraint (all P < 0.05). Collectively, our findings suggest age and sex have significant impacts on Wb, operating lung volumes, EFL, and dyspnea during exercise. Moreover, it appears that mechanical ventilatory constraint may partially explain sex differences in exertional dyspnea in older individuals. NEW & NOTEWORTHY We found that age and sex have a significant effect on mechanical ventilatory constraint and the perception of dyspnea during exercise. We also observed that the perception of exertional dyspnea is associated with indexes of mechanical ventilatory constraint. Collectively, our results suggest that the combined influences of age and biological sex on mechanical ventilatory constraint during exercise contributes, in part, to the increased perception of dyspnea during exercise in older women. [ABSTRACT FROM AUTHOR]

In addition to dyspnea and fatigue, pain is a prevalent symptom in chronic obstructive pulmonary disease (COPD). Understanding the relative prevalence, magnitude, and interference with aspects of daily living of these symptoms can improve COPD management. Therefore, the purposes of this study were to: (1) compare the prevalence and magnitude of dyspnea, fatigue, and pain and how each limits aspects of daily living; (2) determine the association between pain and the other two symptoms; and (3) assess the impact of these symptoms on quality of life in COPD. Participants were recruited from pulmonary rehabilitation programs. Pain, dyspnea, and fatigue were measured using the Brief Pain Inventory (BPI), Brief Fatigue Inventory (BFI), and Dyspnea Inventory (DI), respectively. Quality of life was measured using the Clinical COPD Questionnaire (CCQ). The prevalence of dyspnea, fatigue, and pain were 93%, 77%, and 74%, respectively. Individuals with COPD reported similar severity scores of the three symptoms. Dyspnea interfered with general activity more than pain (F1.7,79.9= 3.1,p< 0.05), whilst pain interfered with mood (F1.8, 82.7= 3.6,p< 0.05) and sleep (F1,46= 7.4,p< 0.01) more than dyspnea and fatigue. These three symptoms were moderately-to-highly correlated with each other (ρ = 0.49–0.78,p< 0.01) and all individually impacted quality of life. In summary, pain is a common symptom in addition to dyspnea and fatigue in COPD; all three interfere similarly among aspects of daily living with some exceptions. Accordingly, management of COPD should include a multifaceted approach that addresses pain as well as dyspnea and fatigue. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) comprises a large and heterogeneous group of disorders that often lead to progressive fibrosis and premature death. Oxygen supplementation is typically used in patients with advanced lung disease with resting hypoxemia; however, there is a paucity of evidence guiding the use of supplemental oxygen in ILD, and significant heterogeneity in clinical practice. It remains unclear whether supplemental oxygen improves clinically meaningful outcomes, and the role of ambulatory oxygen supplementation in isolated exertional hypoxemia is particularly controversial. In some regions, the lack of robust data creates barriers to funding support and access to supplemental oxygen for patients with ILD. Further research into the role of oxygen supplementation is needed to optimize the comprehensive care of this patient population. [ABSTRACT FROM AUTHOR]