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Background: The precise mechanisms driving poor exercise tolerance in patients with fibrotic interstitial lung diseases (fibrotic ILDs) showing a severe impairment in single-breath lung diffusing capacity for carbon monoxide (DLCO < 40% predicted) are not fully understood. Rather than only reflecting impaired O2 transfer, a severely impaired DLCO may signal deranged integrative physiologic adjustments to exercise that jointly increase the burden of exertional symptoms in fibrotic ILD. Methods: Sixty-seven subjects (46 with idiopathic pulmonary fibrosis, 24 showing DLCO < 40%) and 22 controls underwent pulmonary function tests and an incremental cardiopulmonary exercise test with serial measurements of operating lung volumes and 0-10 Borg dyspnea and leg discomfort scores. Results: Subjects from the DLCO < 40% group showed lower spirometric values, more severe restriction, and lower alveolar volume and transfer coefficient compared to controls and participants with less impaired DLCO (P < .05). Peak work rate was -45% (vs controls) and -20% (vs DLCO > 40%) lower in the former group, being associated with lower (and flatter) O2 pulse, an earlier lactate (anaerobic) threshold, heightened submaximal ventilation, and lower SpO2 . Moreover, critically high inspiratory constrains were reached at lower exercise intensities in the DLCO < 40% group (P < .05). In association with the greatest leg discomfort scores, they reported the highest dyspnea scores at a given work rate. Between-group differences lessened or disappeared when dyspnea intensity was related to indexes of increased demand-capacity imbalance, that is, decreasing submaximal, dynamic ventilatory reserve, and inspiratory reserve volume/total lung capacity (P > .05). Conclusions: A severely reduced DLCO in fibrotic ILD signals multiple interconnected derangements (cardiovascular impairment, an early shift to anaerobic metabolism, excess ventilation, inspiratory constraints, and hypoxemia) that ultimately lead to limiting respiratory (dyspnea) and peripheral (leg discomfort) symptoms. DLCO < 40%, therefore, might help in clinical decision-making to indicate the patient with fibrotic ILD who might derive particular benefit from pharmacologic and non-pharmacologic interventions aimed at lessening these systemic abnormalities. [ABSTRACT FROM AUTHOR]

Following pulmonary embolism (PE), a third of patients develop persistent dyspnea, which is commonly termed the post-PE syndrome. The neurophysiological underpinnings of exertional dyspnea in patients with post-PE syndrome without pulmonary hypertension (PH) are unclear. Thus, the current study determined if abnormally high inspiratory neural drive (IND) due, in part, to residual pulmonary gas-exchange abnormalities, was linked to heightened exertional dyspnea and exercise limitation, in such patients. Fourteen participants with post-PE syndrome (without resting PH) and 14 age-, sex-, and body mass index-matched healthy controls undertook pulmonary function testing and a symptom-limited cycle cardiopulmonary exercise test with measurements of IND (diaphragmatic electromyography), ventilatory requirements for CO2 (VE/VCO2), and perceived dyspnea intensity (modified Borg 0-10 scale). Post-PE (vs. control) had a reduced resting transfer coefficient for carbon monoxide (KCO: 84 ± 15 vs. 104 ± 14%pred, P < 0.001) and peak oxygen uptake (VO2peak) (76 ± 14 vs. 124 ± 28%pred, P < 0.001). IND and VE/VCO2 were higher in post-PE than controls at standardized submaximal work rates (P < 0.05). Dyspnea increased similarly in both groups as a function of increasing IND but was higher in post-PE at standardized submaximal work rates (P < 0.05). High IND was associated with low KCO (r = -0.484, P < 0.001), high VE/VCO2 nadir (r = 0.453, P < 0.001), and low VO2peak (r = -0.523, P < 0.001). In patients with post-PE syndrome, exercise IND was higher than controls and was associated with greater dyspnea intensity. The heightened IND and dyspnea in post-PE, in turn, were strongly associated with low resting KCO and high exercise VE/VCO2, which suggest important pulmonary gas-exchange abnormalities in this patient population. NEW & NOTEWORTHY This study is the first to show that increased exertional dyspnea in patients with post-pulmonary embolism (PE) syndrome, without overt pulmonary hypertension, was strongly associated with elevated inspiratory neural drive (IND) to the diaphragm during exercise, compared with healthy controls. The greater IND was associated with impairments in pulmonary gas exchange and significant deconditioning. Our results help to explain why many patients with post-PE syndrome report significant dyspnea at relatively low levels of physical activity. [ABSTRACT FROM AUTHOR]

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]

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]

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]

Patients with mild chronic obstructive pulmonary disease (COPD) and lower resting diffusing capacity for carbon monoxide (DLCO) often report troublesome dyspnea during exercise although the mechanisms are not clear. We postulated that in such individuals, exertional dyspnea is linked to relatively high inspiratory neural drive (IND) due, in part, to the effects of reduced ventilatory efficiency. This cross-sectional study included 28 patients with GOLD I COPD stratified into two groups with (n = 15) and without (n = 13) DLCO less than the lower limit of normal (2 (V̇E/V̇CO2), and respiratory mechanics during incremental cycle exercise in the three groups. Spirometry and resting lung volumes were similar between COPD groups. During exercise, dyspnea, IND and V̇E/V̇CO2 were higher at equivalent work rates (WR) in the DLCOCOCOCOE/V̇CO2 at a given work rate. Higher ventilatory requirements in the DLCO

Background and objective: The combination of both reduced resting diffusing capacity of the lung for carbon monoxide (DLCO) and ventilatory efficiency (increased ventilatory requirement for CO2 clearance [V˙E/V˙CO2]) has been linked to exertional dyspnoea and exercise intolerance in chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are poorly understood. The current study examined if low resting DLCO and higher exercise ventilatory requirements were associated with earlier critical dynamic mechanical constraints, dyspnoea and exercise limitation in patients with mild COPD. Methods: In this retrospective analysis, we compared V˙E/V˙CO2, dynamic inspiratory reserve volume (IRV), dyspnoea and exercise capacity in groups of patients with Global Initiative for Chronic Obstructive Lung Disease stage 1 COPD with (1) a resting DLCO at or greater than the lower limit of normal (≥LLN; Global Lung Function Initiative reference equations [n = 44]) or (2) below the

Background: COPD is associated with nighttime respiratory symptoms, poor sleep quality, and increased risk of nocturnal death. Overnight deterioration of inspiratory capacity (IC) and FEV1 have been documented previously. However, the precise nature of this deterioration and mechanisms by which evening bronchodilation may mitigate this occurrence have not been studied.Research Question: What is the effect of evening dosing of dual, long-acting bronchodilation on detailed nocturnal respiratory mechanics and inspiratory neural drive (IND)?Study Design and Methods: A double-blind, randomized, placebo-controlled crossover study assessed the effects of evening long-acting bronchodilation (aclidinium bromide/formoterol fumarate dihydrate: 400/12 μg) or placebo on morning trough IC (12 h after the dose; primary outcome) and serial overnight measurements of spirometry, dynamic respiratory mechanics, and IND (secondary outcomes). Twenty participants with COPD (moderate/severe airway obstruction and lung hyperinflation) underwent serial measurements of IC, spirometry, breathing pattern, esophageal and transdiaphragmatic pressures, and diaphragm electromyography (diaphragmatic electromyography as a percentage of maximum; IND) at 6 time points from 0 to 12 h after the dose and compared with sleeping IND.Results: Compared with placebo, evening bronchodilation was not associated with increased morning trough IC 12 h after the dose (P = .48); however, nadir IC (lowest IC, independent of time), peak IC, area under the curve for 12 h after the dose, and IC for 10 h after the dose were improved (P < .05). During placebo, total airways resistance, lung hyperinflation, IND, and tidal esophageal and transdiaphragmatic pressure swings all increased significantly overnight compared with baseline evening values; however, each of these parameters improved with bronchodilator treatment (P < .05) with no change in ventilation or breathing pattern.Interpretation: Respiratory mechanics significantly deteriorated at night during placebo. Although the morning trough IC was unchanged, evening bronchodilator treatment was associated consistently with sustained overnight improvements in dynamic respiratory mechanics and inspiratory neural drive compared with placebo CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02429765. [ABSTRACT FROM AUTHOR]

Dyspnea is the most common symptom experienced by patients with chronic obstructive pulmonary disease (COPD). To avoid exertional dyspnea, many patients adopt a sedentary lifestyle which predictably leads to extensive skeletal muscle deconditioning, social isolation, and its negative psychological sequalae. This "dyspnea spiral" is well documented and it is no surprise that alleviation of this distressing symptom has become a key objective highlighted across COPD guidelines. In reality, this important goal is often difficult to achieve, and successful symptom management awaits a clearer understanding of the underlying mechanisms of dyspnea and how these can be therapeutically manipulated for the patients' benefit. Current theoretical constructs of the origins of activity-related dyspnea generally endorse the classical demand-capacity imbalance theory. Thus, it is believed that disruption of the normally harmonious relationship between inspiratory neural drive (IND) to breathe and the simultaneous dynamic response of the respiratory system fundamentally shapes the expression of respiratory discomfort in COPD. Sadly, the symptom of dyspnea cannot be eliminated in patients with advanced COPD with relatively fixed pathophysiological impairment. However, there is evidence that effective symptom palliation is possible for many. Interventions that reduce IND, without compromising alveolar ventilation (VA), or that improve respiratory mechanics and muscle function, or that address the affective dimension, achieve measurable benefits. A common final pathway of dyspnea relief and improved exercise tolerance across the range of therapeutic interventions (bronchodilators, exercise training, ambulatory oxygen, inspiratory muscle training, and opiate medications) is reduced neuromechanical dissociation of the respiratory system. These interventions, singly and in combination, partially restore more harmonious matching of excessive IND to ventilatory output achieved. In this review we propose, on the basis of a thorough review of the recent literature, that effective dyspnea amelioration requires combined interventions and a structured multidisciplinary approach, carefully tailored to meet the specific needs of the individual. [ABSTRACT FROM AUTHOR]

The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (DLCO) to dyspnea and exercise intolerance across the chronic obstructive pulmonary disease (COPD) continuum are poorly understood. COPD progression generally involves both DLCO decline and worsening respiratory mechanics, and their relative contribution to dyspnea has not been determined. In a retrospective analysis of 300 COPD patients who completed symptom-limited incremental cardiopulmonary exercise tests, we tested the association between peak oxygen-uptake (VO2), DLCO, and other resting physiological measures. Then, we stratified the sample into tertiles of forced expiratory volume in 1 s (FEV1) and inspiratory capacity (IC) and compared dyspnea ratings, pulmonary gas exchange, and respiratory mechanics during exercise in groups with normal and low DLCO [i.e., CO was associated with peak VO2 (P = 0.006), peak work-rate (P = 0.005), and dyspnea/VO2 slope (P < 0.001) after adjustment for other independent variables (airway obstruction and hyperinflation). Within FEV1 and IC tertiles, peak VO2 and work rate were lower (P = 0.05) in low versus normal DLCO groups. Across all tertiles, low DLCO groups had higher dyspnea ratings, greater ventilatory inefficiency and arterial oxygen desaturation, and showed greater mechanical volume constraints at a lower ventilation during exercise than the normal DLCO group (all P < 0.05). After accounting for baseline resting respiratory mechanical abnormalities, DLCOCO. The higher dyspnea ratings and earlier exercise termination in low DLCO groups were linked to significantly greater pulmonary gas exchange abnormalities, higher ventilatory demand, and associated accelerated dynamic mechanical constraints. NEW & NOTEWORTHY Our study demonstrated that chronic obstructive pulmonary disease patients with diffusing capacity of the lung for carbon monoxide (DLCO) less than the lower limit of normal had greater pulmonary gas exchange abnormalities, which resulted in higher ventilatory demand and greater dynamic mechanical constraints at lower ventilation during exercise. This, in turn, led to greater exertional dyspnea and exercise intolerance compared with patients with normal DLCO. [ABSTRACT FROM AUTHOR]

Supervised exercise training (EXT) as part of pulmonary rehabilitation is arguably the most effective intervention for improving exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). In the current review, we focus on the physiological rationale for EXT and the expected physiological benefits that can be achieved in patients who can be exposed to sufficiently high training stimuli. Thus, after a brief consideration of the mechanisms of exercise limitation and their sensory consequences, we expose the potential beneficial effects of EXT on respiratory mechanical and peripheral muscular adaptations to exercise. The available evidence indicates that changes in exertional ventilation, breathing pattern, operating lung volumes and static respiratory muscle strength after EXT are modest and often inconsistent. Inspiratory muscle training may have a role in patients showing inspiratory weakness pre-rehabilitation. Beneficial changes in peripheral muscles can be seen in those who can tolerate higher training intensity, particularly using combined resistance and dynamic (including interval) exercise. It should be recognised, however, that it might not be feasible to reach meaningful physiological training effects in many frail elderly patients with advanced respiratory mechanical and pulmonary gas exchange derangements with serious co-morbidities (such as cardiac and peripheral vascular disease). These potential shortcomings should not discourage the use of pulmonary rehabilitation as an effective strategy to improve patients' capacity to tolerate physical activity. Currently, the greatest challenge is to develop effective strategies to ensure that these important gains in functional capacity are translated into sustained increases in daily physical activity for patients with COPD. [ABSTRACT FROM AUTHOR]

The article describes how forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio discordance relates to functional outcomes relevant to subjects' daily functioning. Topics include the fixed FEV1/FVC ratio cutoff can result in over diagnosis of Chronic obstructive pulmonary disease (COPD) in older individuals; and a discordant FEV1/FVC ratio should be individually interpreted in light of clinical data.

ABSTRACT Background and objective Frailty is the age-related accumulation of deficits that decrease the ability to respond to biological stress. Patients with fibrotic interstitial lung disease ( ILD) may be frail due to consequences of ILD, age, co-morbidities and adverse effects of pharmacotherapies. The objective of this study was to examine the prevalence and predictors of frailty in fibrotic ILD. Methods Fibrotic ILD patients were recruited from a specialized clinic. Patients with ILD secondary to a systemic disease were excluded. Frailty was determined using the Frailty Index based on the presence or absence of multiple deficits, including co-morbidities, symptoms and functional limitations. The Frailty Index was based on the proportion of deficits present, with frailty defined as a score >0.21. Cronbach's alpha was used to estimate the internal consistency of the Frailty Index. Dyspnoea was measured using the University of California San Diego Shortness of Breath Questionnaire. Multivariate analysis was used to determine independent predictors of frailty. Results The definition of frailty was met in 50% of the 129 patients. Cronbach's alpha for the Frailty Index was 0.87. The Frailty Index was associated with forced vital capacity ( FVC), forced expiratory volume in 1 s ( FEV1 ), diffusion capacity of the lung for carbon monoxide ( DLCO ), ILD-gender, age and physiology ( GAP) index, composite physiologic index and dyspnoea score. Dyspnoea severity was the strongest unadjusted predictor (r = 0.65, P < 0.001) and only independent predictor of the Frailty Index (0.034 increase in Frailty Index per 10-point increase in dyspnoea score; R2 = 0.37; P < 0.001). Conclusion Frailty is highly prevalent and is strongly and independently associated with dyspnoea severity, demonstrating that dyspnoea is a more important determinant of frailty than pulmonary function. [ABSTRACT FROM AUTHOR]

Patients with mild chronic obstructive pulmonary disease (COPD) and lower resting diffusing capacity for carbon monoxide (DLCO) often report troublesome dyspnea during exercise although the mechanisms are not clear. We postulated that in such individuals, exertional dyspnea is linked to relatively high inspiratory neural drive (IND) due, in part, to the effects of reduced ventilatory efficiency. This cross-sectional study included 28 patients with GOLD I COPD stratified into two groups with (n = 15) and without (n = 13) DLCO less than the lower limit of normal (

Background: The precise mechanisms driving poor exercise tolerance in patients with fibrotic interstitial lung diseases (fibrotic ILDs) showing a severe impairment in single-breath lung diffusing capacity for carbon monoxide (D LCO < 40% predicted) are not fully understood. Rather than only reflecting impaired O 2 transfer, a severely impaired D LCO may signal deranged integrative physiologic adjustments to exercise that jointly increase the burden of exertional symptoms in fibrotic ILD., Methods: Sixty-seven subjects (46 with idiopathic pulmonary fibrosis, 24 showing D LCO < 40%) and 22 controls underwent pulmonary function tests and an incremental cardiopulmonary exercise test with serial measurements of operating lung volumes and 0-10 Borg dyspnea and leg discomfort scores., Results: Subjects from the D LCO < 40% group showed lower spirometric values, more severe restriction, and lower alveolar volume and transfer coefficient compared to controls and participants with less impaired D LCO ( P < .05). Peak work rate was ∼45% (vs controls) and ∼20% (vs D LCO > 40%) lower in the former group, being associated with lower (and flatter) O 2 pulse, an earlier lactate (anaerobic) threshold, heightened submaximal ventilation, and lower S pO 2 . Moreover, critically high inspiratory constrains were reached at lower exercise intensities in the D LCO < 40% group ( P < .05). In association with the greatest leg discomfort scores, they reported the highest dyspnea scores at a given work rate. Between-group differences lessened or disappeared when dyspnea intensity was related to indexes of increased demand-capacity imbalance, that is, decreasing submaximal, dynamic ventilatory reserve, and inspiratory reserve volume/total lung capacity ( P > .05)., Conclusions: A severely reduced D LCO in fibrotic ILD signals multiple interconnected derangements (cardiovascular impairment, an early shift to anaerobic metabolism, excess ventilation, inspiratory constraints, and hypoxemia) that ultimately lead to limiting respiratory (dyspnea) and peripheral (leg discomfort) symptoms. D LCO < 40%, therefore, might help in clinical decision-making to indicate the patient with fibrotic ILD who might derive particular benefit from pharmacologic and non-pharmacologic interventions aimed at lessening these systemic abnormalities., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2023 by Daedalus Enterprises.)

Objectives: Dyspnoea is a common persistent symptom post-coronavirus disease 2019 (COVID-19) illness. However, the mechanisms underlying dyspnoea in the post-COVID-19 syndrome remain unclear. The aim of our study was to examine dyspnoea quality and intensity, burden of mental health symptoms, and differences in exercise responses in people with and without persistent dyspnoea following COVID-19., Methods: 49 participants with mild-to-critical COVID-19 were included in this cross-sectional study 4 months after acute illness. Between-group comparisons were made in those with and without persistent dyspnoea (defined as modified Medical Research Council dyspnoea score ≥1). Participants completed standardised dyspnoea and mental health symptom questionnaires, pulmonary function tests, and incremental cardiopulmonary exercise testing., Results: Exertional dyspnoea intensity and unpleasantness were increased in the dyspnoea group. The dyspnoea group described dyspnoea qualities of suffocating and tightness at peak exercise (p<0.05). Ventilatory equivalent for carbon dioxide ( V ' E / V ' CO 2 ) nadir was higher (32±5 versus 28±3, p<0.001) and anaerobic threshold was lower (41±12 versus 49±11% predicted maximum oxygen uptake, p=0.04) in the dyspnoea group, indicating ventilatory inefficiency and deconditioning in this group. The dyspnoea group experienced greater symptoms of anxiety, depression and post-traumatic stress (all p<0.05). A subset of participants demonstrated gas-exchange and breathing pattern abnormalities suggestive of dysfunctional breathing., Conclusions: People with persistent dyspnoea following COVID-19 experience a specific dyspnoea quality phenotype. Dyspnoea post-COVID-19 is related to abnormal pulmonary gas exchange and deconditioning and is linked to increased symptoms of anxiety, depression and post-traumatic stress., Competing Interests: Conflict of interest: K.L. Lavoie reports consulting fees from AbbVie, Takeda, Astellas, Boehringer Ingelheim, AstraZeneca, Janssen, Novartis, GSK, Bausch and Sojecci Inc., outside the submitted work; payment or honoraria from AbbVie, Boehringer Ingelheim, Takeda, Pfizer, Merck, GSK, Astra-Zeneca, Novartis, Janssen, Bayer, Mundi Pharma, Bayer, Air Liquide, Astellas and Xfacto, outside the submitted work; and participation on a Data Safety Monitoring Board or Advisory Board for Astra-Zeneca, GSK and Bausch, outside the submitted work. Conflict of interest: J. Cowan reports support for the present manuscript from The Ottawa Hospital Foundation; grants or contracts from Octapharma and Takeda, outside the submitted work; payment or honoraria from GSK, Sanofi, EMD Serono, Alexion and Takeda, outside the submitted work; and support for attending meetings and/or travel from Octapharma, outside the submitted work. Conflict of interest: J.A. Chirinos reports grants or contracts from University of Pennsylvania research grants from National Institutes of Health, Fukuda-Denshi, Bristol-Myers Squibb, Microsoft and Abbott, outside the submitted work; consulting fees from Bayer, Sanifit, Fukuda-Denshi, Bristol-Myers Squibb, JNJ, Edwards Life Sciences, Merck, NGM Biopharmaceuticals and the Galway-Mayo Institute of Technology, outside the submitted work; patents planned, issued or pending: inventor in a University of Pennsylvania patent for the use of inorganic nitrates/nitrites for the treatment of Heart Failure and Preserved Ejection Fraction and for the use of biomarkers in heart failure with preserved ejection fraction, outside the submitted work; participant on advisory board for BMS, outside the submitted work; Vice President of North American Artery Society, outside the submitted work; received research device loans from Atcor Medical, Fukuda-Denshi, Uscom, NDD Medical Technologies, Microsoft and MicroVision Medical, outside the submitted work; received payments for editorial roles from the American Heart Association, the American College of Cardiology and Wiley, outside the submitted work. Conflict of interest: J.A. Guenette is an associate editor of this journal. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Patients with mild chronic obstructive pulmonary disease (COPD) and lower resting diffusing capacity for carbon monoxide (DL CO ) often report troublesome dyspnea during exercise although the mechanisms are not clear. We postulated that in such individuals, exertional dyspnea is linked to relatively high inspiratory neural drive (IND) due, in part, to the effects of reduced ventilatory efficiency. This cross-sectional study included 28 patients with GOLD I COPD stratified into two groups with ( n  = 15) and without ( n  = 13) DL CO less than the lower limit of normal (2 ( V̇ E / V̇ CO 2 ), and respiratory mechanics during incremental cycle exercise in the three groups. Spirometry and resting lung volumes were similar between COPD groups. During exercise, dyspnea, IND and V̇ E / V̇ CO 2 were higher at equivalent work rates (WR) in the DL CO CO CO CO E / V̇ CO 2 at a given work rate. Higher ventilatory requirements in the DL CO

Many patients with severe chronic obstructive pulmonary disease (COPD) report an unpleasant respiratory sensation at rest, which is further amplified by adoption of a supine position (orthopnoea). The mechanisms of this acute symptomatic deterioration are poorly understood.Sixteen patients with advanced COPD and a history of orthopnoea and 16 age- and sex-matched healthy controls underwent pulmonary function tests (PFTs) and detailed sensory-mechanical measurements including inspiratory neural drive (IND) assessed by diaphragm electromyography (EMG di ), oesophageal pressure ( P es ) and gastric pressure ( P ga ), in both sitting and supine positions.Patients had severe airflow obstruction (forced expiratory volume in 1 s (FEV 1 ): 40±18% pred) and lung hyperinflation. Regardless of the position, patients had lower inspiratory capacity (IC) and higher IND for a given tidal volume ( V T ) ( i.e. greater neuromechanical dissociation (NMD)), higher intensity of breathing discomfort, higher minute ventilation ( V ' E ) and higher breathing frequency ( f B ) compared with controls (all p<0.05). For controls in a supine position, IC increased by 0.48 L versus sitting erect, with a small drop in V ' E , mainly due to reduced f B (all p<0.05). By contrast, IC remained unaltered in patients with COPD, but dynamic lung compliance ( C Ldyn ) decreased (p<0.05) in the supine position. Breathing discomfort, inspiratory work of breathing (WOB), inspiratory effort, IND, NMD and neuroventilatory uncoupling all increased in COPD patients in the supine position (p<0.05), but not in the healthy controls. Orthopnoea was associated with acute changes in IND (r=0.65, p=0.01), neuroventilatory uncoupling (r=0.76, p=0.001) and NMD (r=0.73, p=0.002).In COPD, onset of orthopnoea coincided with an abrupt increase in elastic loading of the inspiratory muscles in recumbency, in association with increased IND and greater NMD of the respiratory system., Competing Interests: Conflict of interest: A.F. Elbehairy has nothing to disclose. Conflict of interest: A. Faisal has nothing to disclose. Conflict of interest: H. McIsaac has nothing to disclose. Conflict of interest: N.J. Domnik has nothing to disclose. Conflict of interest: K.M. Milne has nothing to disclose. Conflict of interest: M.D. James has nothing to disclose. Conflict of interest: J.A. Neder has nothing to disclose. Conflict of interest: D.E. O'Donnell has nothing to disclose., (Copyright ©ERS 2021.)

Assessment of the ventilatory response to exercise is important in evaluating mechanisms of dyspnea and exercise intolerance in chronic cardiopulmonary diseases. The characteristic mechanical derangements that occur during exercise in chronic respiratory conditions have previously been determined in seminal studies using esophageal catheter pressure-derived measurements. In this brief review, we examine the emerging role and clinical utility of conventional assessment of dynamic respiratory mechanics during exercise testing. Thus, we provide a physiologic rationale for measuring operating lung volumes, breathing pattern, and flow-volume loops during exercise. We consider standardization of inspiratory capacity-derived measurements and their practical implementation in clinical laboratories. We examine the evidence that this iterative approach allows greater refinement in evaluation of ventilatory limitation during exercise than traditional assessments of breathing reserve. We appraise the available data on the reproducibility and responsiveness of this methodology. In particular, we review inspiratory capacity measurement and derived operating lung volumes during exercise. We demonstrate, using recent published data, how systematic evaluation of dynamic mechanical constraints, together with breathing pattern analysis, can provide valuable insights into the nature and extent of physiological impairment contributing to exercise intolerance in individuals with common chronic obstructive and restrictive respiratory disorders., (Copyright © 2020 Milne, Domnik, Phillips, James, Vincent, Neder and O'Donnell.)

Lung function testing has undisputed value in the comprehensive assessment and individualized management of chronic obstructive pulmonary disease, a pathologic condition in which a functional abnormality, poorly reversible expiratory airway obstruction, is at the core of its definition. After an overview of the physiologic underpinnings of the disease, the authors outline the role of lung function testing in this disease, including diagnosis, assessment of severity, and indication for and responses to pharmacologic and nonpharmacologic interventions. They discuss the current controversies surrounding test interpretation with these purposes in mind and provide balanced recommendations to optimize their usefulness in different clinical scenarios., Competing Interests: Disclosure The authors have no conflict of interest to disclose relative to the subject matter or materials discussed in this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The majority of smokers with chronic obstructive pulmonary disease (COPD) have mild airflow limitation as determined by simple spirometry. Although small airway dysfunction is the hallmark of COPD, many studies attest to complex heterogeneous physiological impairments beyond increased airway resistance. These impairments are related to inflammation of lung parenchyma and its microvasculature, which is obscured by simple spirometry. Recent studies using advanced radiological imaging have highlighted significant structural abnormalities in smokers with relatively preserved spirometry. These important studies have generated considerable interest and have reinforced the pressing need to better understand the physiological consequences of various morphological abnormalities, and their impact on the clinical outcomes and natural history of COPD. The overarching objective of this review is to provide a concise overview of the importance and utility of cardiopulmonary exercise testing (CPET) in clinical and research settings. CPET uniquely allows evaluation of integrated abnormalities of the respiratory, cardio-circulatory, metabolic, peripheral muscle and neurosensory systems during increases in physiologic stress. This brief review examines the results of recent studies in mild COPD that have uncovered consistent derangements in pulmonary gas exchange and development of "restrictive" dynamic mechanics that together contribute to exercise intolerance. We examine the evidence that compensatory increases in inspiratory neural drive from respiratory control centers are required during exercise in mild COPD to maintain ventilation commensurate with increasing metabolic demand. The ultimate clinical consequences of this high inspiratory neural drive are earlier onset of critical respiratory mechanical constraints and increased perceived respiratory discomfort at relatively low exercise intensities., (Copyright © 2020 James, Milne, Phillips, Neder and O'Donnell.)

Dyspnea, the most common symptom in chronic obstructive pulmonary disease (COPD), often becomes disabling in advanced stages of the disease. Chronic dyspnea erodes perceived health status and diminishes engagement in physical activity, often leading to skeletal muscle deconditioning, anxiety, depression, and social isolation. Broader understanding of the pathophysiologic underpinnings of dyspnea has allowed us to formulate a sound rationale for individualized management. This review examines recent research and provides historical context. The overarching objectives are to consider current constructs of the physiologic mechanisms of activity-related dyspnea and identify specific targets amenable to therapeutic manipulation in patients with COPD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Unexplained dyspnea presents a significant diagnostic challenge. Dyspnea arises when inspiratory neural drive (IND) to the respiratory muscles is increased and the respiratory system fails to meet this increased demand. Cardiopulmonary exercise testing (CPET) is a valuable tool to unravel the causes of exertional dyspnea in the individual. Moreover, analysis of breathing pattern, operating lung volumes and flow-volume loops allows characterization of abnormal dynamic mechanical response to increased IND - an important source of breathing discomfort. We illustrate the clinical utility of this approach which examines respiratory sensation, ventilatory control, respiratory mechanics and cardio-circulatory responses in cases of unexplained dyspnea., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Narrative reviews are frequently accessed; however, the content and quality of review articles on idiopathic pulmonary fibrosis (IPF) have not been assessed. A systematic review assessed content and quality of narrative review articles that addressed the diagnosis or management of IPF and were published from 2001 to 2015. Article recommendations were assessed relative to contemporary IPF guidelines. Quality was assessed using the DISCERN instrument. Articles were predominantly written by physicians and published in respiratory journals. Conflicts of interest and sources of funding were reported in 52% and 24% of reviews, respectively. European authors were more likely to recommend bronchoscopy (adjusted p=0.02) and were more likely to recommend pirfenidone or nintedanib prior to publication of definitive clinical trials (adjusted p=0.04). A total of 39% of management-focused articles suggested therapies that were never recommended in guidelines. Predictors of higher article quality were citation of the contemporary IPF guideline (p=0.01) and more recent publication (p=0.001). Quality of reviews increased over time; however, review articles frequently made discordant recommendations compared to IPF guidelines. These findings indicate the need for authors, peer reviewers, editors and readers to critically appraise the content and quality of narrative reviews on IPF, and the need for frequent guideline updates to reflect new evidence., Competing Interests: Conflict of interest: K.M. Milne has nothing to disclose. Conflict of interest: C. Chan has nothing to disclose. Conflict of interest: J.H. Fisher has nothing to disclose. Conflict of interest: K. de Boer reports grants and personal fees from Boehringer Ingelheim, and personal fees from Hoffmann-La Roche and AstraZeneca, outside the submitted work. Conflict of interest: C.J. Ryerson reports grants and personal fees from Boehringer Ingelheim and Hoffmann-La Roche, outside the submitted work.