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Exertional dyspnoea is among the dominant symptoms in patients with chronic heart failure and progresses relentlessly as the disease advances, leading to reduced ability to function and engage in activities of daily living. Effective management of this disabling symptom awaits a better understanding of its underlying physiology.Cardiovascular factors are believed to play a major role in dyspnoea in heart failure patients. However, despite pharmacological interventions, such as vasodilators or inotropes that improve central haemodynamics, patients with heart failure still complain of exertional dyspnoea. Clearly, dyspnoea is not determined by cardiac factors alone, but likely depends on complex, integrated cardio-pulmonary interactions.A growing body of evidence suggests that excessively increased ventilatory demand and abnormal "restrictive" constraints on tidal volume expansion with development of critical mechanical limitation of ventilation, contribute to exertional dyspnoea in heart failure. This article will offer new insights into the pathophysiological mechanisms of exertional dyspnoea in patients with chronic heart failure by exploring the potential role of the various constituents of the physiological response to exercise and particularly the role of abnormal ventilatory and respiratory mechanics responses to exercise in the perception of dyspnoea in patients with heart failure., (Copyright ©ERS 2016.)

Background: The relevance of screening for airway obstruction in subjects not complaining of COPD symptoms may depend on the definition of airway obstruction. Response to exercise in asymptomatic subjects with persistent airway obstruction as defined by a postbronchodilator FEV1/FVC <5th centile lower limit of normal (LLN) remains unknown., Methods: Dyspnoea (Borg scale), exercise tolerance and ventilatory constraints on tidal volume expansion were assessed in 20 consecutive asymptomatic subjects with persistent mild airway obstruction detected by screening (postbronchodilator FEV1/FVC z-score: -2.14±0.29; FEV1 z-score: -1.02±0.64) undergoing incremental cycle cardiopulmonary exercise testing, compared with 20 healthy controls with normal spirometry matched for age, sex, body mass index and smoking history (FEV1/FVC z-score: -0.13±0.57; FEV1 z-score: 0.32±0.67) and with 20 symptomatic patients with COPD matched for the same characteristics (FEV1/FVC z-score: -2.36±0.51; FEV1 z-score: -1.02±0.48)., Results: Asymptomatic subjects with airway obstruction had higher dyspnoea ratings than controls during incremental exercise. Asymptomatic subjects with airway obstruction had also peak oxygen consumption and peak power output that were lower than controls, and similar to those observed in patients with COPD. Although less frequent than in COPD, dynamic hyperinflation was more frequent in asymptomatic subjects with airway obstruction than in controls (85%, 50% and 10%, respectively; p=0.01 in asymptomatic subjects vs controls and p=0.04 vs COPD)., Conclusions: Although they did not present with chronic activity-related dyspnoea, subjects with a postbronchodilator FEV1/FVC

Limitation of activity is the most cited symptom described by uncontrolled asthma patients. Assessment of activity limitation can be undertaken through several ways, more or less complex, subjective or objective. Yet little is known about the link between patients sensations and objective measurements. The present review reports the current knowledge regarding activity limitation and symptom perception (i.e., exertional dyspnea) in adult patients with asthma. This work is based on references indexed by PubMed, irrespective of the year of publication. Overall, patients with stable asthma do not have a more sedentary lifestyle than healthy subjects. However, during a cycle ergometric test, the maximal load is reduced when FEV1, FVC and muscle strengths are decreased. Additionally, during the six-minute walking test, mild asthma patients walk less than healthy subjects even if the minimal clinically important difference is not reached. The major complaint of asthma patients when exercising is dyspnea that is mainly related to the inspiratory effort and also to dynamic hyperinflation in some circumstances. Finally, the administration of bronchodilator does not improve the ventilatory pattern and the exercise capacity of asthma patients and little is known on its effect on exertional dyspnea. The present review allows to conclude that until now there is no gold standard test allowing the objective assessment of "activity limitation and exertional dyspnea" in asthma patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Combined diffusion capacity of the lung for carbon monoxide (DLco) and nitric oxide (DLno) measurements allow for the estimation of pulmonary capillary blood volume (Vc) and alveolar membrane diffusion (Dm). The clinical usefulness of these measurements in pulmonary hypertension (PH) is unclear., Methods: Combined DLco and DLno were measured in 290 consecutive patients with precapillary PH (pulmonary arterial hypertension (PAH), n = 153; pulmonary veno-occlusive disease (PVOD), n = 33; and chronic thromboembolic pulmonary hypertension (CTEPH), n = 104). Clinical correlates of Vc and Dm were assessed in a sub-group of PAH patients without comorbidities., Results: PVOD patients compared with PAH and CTEPH patients displayed the lowest values of Vc (29.4 ± 16.8 ml vs 56.3 ± 26.5 ml vs 56.9 ± 26.2 ml, p < 0.01, respectively) and Dm (27.7 ± 11.6 ml/mm Hg/min vs 43.4 ± 14.8 ml/mm Hg/min vs 44.7 ± 17.7 ml/mm Hg/min, p < 0.01, respectively). The DLno/DLco ratio was highest in the PVOD group (5.82 ± 2.04 vs 4.95 ± 1.31 vs 5.16 ± 1.58, p < 0.05). In a sub-set of 69 PAH patients without comorbidities, Vc and Dm correlated significantly with functional capacity (6-minute walking distance, oxygen consumption) and New York Heart Association Functional Classification but not with invasive hemodynamics. Only Dm was significantly associated with survival. On receiver operating characteristic curve analysis, Vc, Dm, and DLno/DLco were not superior to DLco for discriminating PVOD from PAH or CTEPH., Conclusions: PVOD patients display higher values of the DLno/DLco ratio compared with PAH and CTEPH, suggesting proportionally greater reduction in Vc relative to Dm. However, partitioning of diffusion failed to be more clinically relevant than conventional DLco for detection of PVOD., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The best clinical practice to investigate aerobic fitness includes measurements obtained during cardiopulmonary exercise testing (CPET), however it remains an underutilised clinical measure in cystic fibrosis (CF). To investigate this further, different methods of quantifying exercise capacity in CF are required. The possibility that measuring physical activity (PA) by a portable accelerometer could be used to assess the CF aerobic state and could be added among the CPET surrogates has not been investigated. The aim of this study was to examine the relationship between PA and exercise fitness both at submaximal and maximal levels in clinically stable adults with CF., Methods: Thirty CF patients (FEV1 71 ± 19% predicted) and fifteen healthy controls undertook an incremental CPET on a cycle ergometer. CPET-related measurements included: oxygen uptake (V'O2), carbon dioxide production (V'CO2), ventilatory profile, heart rate (HR) and oxygen pulse (V'O2/HR) throughout exercise and at lactic threshold (LT) and peak. LT measures represent submaximal exercise related data. PA was assessed using the accelerometer SenseWear Pro3 Armband., Results: Moderate (>4.8 metabolic equivalents (METS)) and moderate + vigorous (>7.2 METS) PA was related to V'O2 (p = 0.005 and p = 0.009, respectively) and work rate (p = 0.004 and p = 0.002, respectively) at LT. Moderate PA or greater was positively related to peak V'O2 (p = 0.005 and p = 0.003, respectively). Daily PA levels were similar in CF and healthy controls. Except for peak values, V'O2 profile and the V'O2 at LT were comparable between CF and healthy controls., Conclusions: In adult CF patients daily PA positively correlated with aerobic capacity. PA measurements are a valuable tool in the assessment of exercise performance in an adult CF population and could be used for interventional exercise trials to optimize exercise performance and health status. PA levels and parameters obtained at submaximal exercise are similar in CF and in healthy controls.

Background: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) coexistence increases morbidity and mortality. The intercept of ventilation (VEint) on the VE vs. carbon dioxide production (VCO2) relationship during exercise has been found to vary in proportion with dead space (VD) in HF. Considering that increased VD is the key pathophysiological abnormality in COPD but a secondary finding in HF we hypothesized that a high VEint would be useful in suggesting COPD as HF co-morbidity. Our aim was to assess whether an elevated VEint suggests the presence of COPD in HF., Methods: In a multicenter retrospective study, the VE-VCO2 relationship was analyzed both as slope and intercept in HF (n = 108), HF-COPD (n = 106) and COPD (n = 95). Patients with pulmonary arterial hypertension (PAH) (n = 85) and healthy subjects (HF) (n = 56) served as positive and negative controls relative to VE-VCO2 abnormalities, respectively., Results: Slope and VEint varied in opposite directions in all groups (p < 0.05) being VE-VCO2 slope highest and lowest in PAH and healthy subjects, respectively. No slope differences were observed among HF, HF-COPD and COPD (32 ± 7, 31 ± 7, and 31 ± 6, respectively). VEint was higher in HF-COPD and COPD compared to HF, PAH and controls (4.8 ± 2.4 L/min, 5.9 ± 3.0 L/min, 3.0 ± 2.6L/min, 2.3 ± 3.3 L/min and 3.9 ± 2.5L/min, respectively; p < 0.01). A VEint ≥ 4.07 L/min identified patients with high probability of having COPD or HF-COPD (sensitivity of 71.6% and specificity of 72.0%)., Conclusion: These data provide novel evidence that a high VEint (≥ 4.07 L/min) should be valued to suggest coexistent COPD in HF patients., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Increased expiratory muscle activity is common during exercise in patients with COPD but its role in modulating operating lung volumes and dyspnea during incremental cycle ergometry is currently unknown. We compared gastric (Pga) and esophageal (Pes) pressures, operating lung volumes and qualitative descriptors of dyspnea during exercise in 12 COPD patients and 12 age- and sex-matched healthy controls. Pes- and Pga-derived measures of expiratory muscle activity were significantly (p<0.05) greater in COPD than in health during exercise. End-expiratory lung volume (EELV) increased by 0.8L, independent of increased expiratory muscle activity in COPD. Dynamic function of the diaphragm was not different in health and COPD throughout exercise. In both groups, dyspnea descriptors alluding to increased work and inspiratory difficulty predominated whereas expiratory difficulty was rarely reported, even at the limits of tolerance. In conclusion, increased expiratory muscle activity did not mitigate the rise in EELV, the relatively early respiratory mechanical constraints or the attendant perceived inspiratory difficulty during exercise in COPD., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Dyspnoea is a debilitating symptom that affects quality of life, exercise tolerance and mortality in various disease conditions/states. In patients with chronic obstructive pulmonary disease (COPD), it has been shown to be a better predictor of mortality than forced expiratory volume in 1 s. In patients with heart disease it is a better predictor of mortality than angina. Dyspnoea is also associated with decreased functional status and worse psychological health in older individuals living at home. It also contributes to the low adherence to exercise training programmes in sedentary adults and in COPD patients. The mechanisms of dyspnoea are still unclear. Recent studies have emphasised the multidimensional nature of dyspnoea in the sensory-perceptual (intensity and quality), affective distress and impact domains. The perception of dyspnoea involves a complex chain of events that depend on varying cortical integration of several afferent/efferent signals and coloured by affective processing. This review, which stems from the European Respiratory Society research symposium held in Paris, France in November 2012, aims to provide state-of-the-art advances on the multidimensional and multidisciplinary aspects of dyspnoea, by addressing three different themes: 1) the neurophysiology of dyspnoea, 2) exercise and dyspnoea, and 3) the clinical impact and management of dyspnoea., (©ERS 2014.)

Peripheral airway dysfunction, inhomogeneous ventilation distribution, gas trapping, and impaired pulmonary gas exchange are variably present in all stages of chronic obstructive pulmonary disease (COPD). This article provides a cogent physiologic explanation for the relentless progression of activity-related dyspnea and exercise intolerance that all too commonly characterizes COPD. The spectrum of physiologic derangements that exist in smokers with mild airway obstruction and a history compatible with COPD is examined. Also explored are the perceptual and physiologic consequences of progressive erosion of the resting inspiratory capacity. Finally, emerging information on the role of cardiocirculatory impairment in contributing to exercise intolerance in patients with varying degrees of airway obstruction is reviewed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Patients with pulmonary arterial hypertension (PAH) may exhibit reduced expiratory flows at low lung volumes, which could promote exercise-induced dynamic hyperinflation (DH). This study aimed to examine the impact of a potential exercise-related DH on the intensity of dyspnoea in patients with PAH undergoing symptom-limited incremental cardiopulmonary cycle exercise testing (CPET). 25 young (aged mean±sd 38±12 yrs) nonsmoking PAH patients with no evidence of spirometric obstruction and 10 age-matched nonsmoking healthy subjects performed CPET to the limit of tolerance. Ventilatory pattern, operating lung volumes (derived from inspiratory capacity (IC) measurements) and dyspnoea intensity (Borg scale) were assessed throughout CPET. IC decreased (i.e. DH) progressively throughout CPET in PAH patients (average 0.15 L), whereas it increased in all the healthy subjects (0.45 L). Among PAH patients, 15 (60%) exhibited a decrease in IC throughout exercise (average 0.50 L), whereas in the remaining 10 (40%) patients IC increased (average 0.36 L). Dyspnoea intensity and ventilation were greater in PAH patients than in controls at any stage of CPET, whereas inspiratory reserve volume was lower. We conclude that DH-induced mechanical constraints and excessive ventilatory demand occurred in these young nonsmoking PAH patients with no spirometric obstruction and was associated with exertional dyspnoea.

Sixteen patients with stable asthma performed a symptom-limited constant work-rate CWR cycle exercise during which breathing pattern, operating lung volumes, dyspnea intensity and its qualitative descriptors were measured. An inflection in the relation between tidal volume (V(T)) and ventilation (V˙(E)) was observed in each subject. The sense of "work/effort" was the dominant dyspnea descriptor selected up to the V(T)/V˙(E) inflection, whereas after it dyspnea intensity and the selection frequency of "unsatisfied inspiration" rose steeply in 37.5% of subjects in whom inspiratory reserve volume (IRV) had decreased to a critical level of 0.6L at the V(T) inflection point. In contrast, dyspnea increased linearly with exercise time and V˙(E), and "work/effort" was the dominant descriptor selected throughout exercise in 62.5% of subjects in whom the V(T)/V˙(E) inflection occurred at a preserved IRV. The V(T) inflection during exercise in patients with stable asthma marked a mechanical event with important sensory consequences only when it occurred at a critical reduced IRV., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Dyspnea and reduced exercise tolerance are common consequences of chronic obstructive pulmonary disease (COPD) and contribute importantly to poor perceived health status. While the origins of dyspnea and reduced exercise tolerance are complex and multifactorial, there is increasing evidence that lung hyperinflation is an important contributory factor that can be targeted for treatment. In this review, the authors summarize current concepts of the origin and clinical and physiological consequences of both static and dynamic lung hyperinflation in COPD. In particular, they review recent studies that have examined the role of lung hyperinflation in dyspnea causation during exacerbations and physical activity in COPD. Finally, current concepts of the mechanisms of symptom relief and improved exercise tolerance following pharmacological lung volume reduction are reviewed.

Unlabelled: Incremental cardiopulmonary exercise test with gas exchange measurement is the gold standard for the identification of the ventilatory compensation point (VCP). It has previously been demonstrated that the change in the slope of increment of minute ventilation over HR (ΔV˙E/ΔHR) can be used alternatively to the ventilatory equivalent for CO₂ (V˙E/V˙CO₂) method for detection of VCP in healthy subjects undergoing cycle ergometer (C) incremental exercise. The same evaluation during treadmill (T) incremental exercise and comparison between C and T have not yet been performed., Purpose: We analyzed, during both C and T incremental exercises, the V˙E/HR and the respiratory rate (RR)/HR relationships, expressed either as slope or as an absolute value. We hypothesized that changes in the slope of increment of the two relationships could represent a reliable method for VCP detection, regardless of exercise mode and protocol., Methods: Fourteen healthy male subjects (age = 31 ± 7 yr (mean ± SD)) underwent two T incremental exercises--fast (FT) and slow (ST) protocols (8 km·h⁻¹, 2% (F(T)) and 1% (S(T)) grade per minute)--and one C incremental exercise (30 W·min⁻¹). O₂ uptake (V˙O₂), V˙CO₂, V˙E, HR, and RR were measured breath by breath., Results: A good between-method agreement in the detection of VCP by the ΔV˙(E)/ΔV˙CO₂, ΔV˙(E)/ΔHR, and the ΔRR/ΔHR slope changes was found in both T protocols and C. No differences (C vs T and F(T) vs S(T)) were found in the slope of the ΔV˙(E)/ΔHR and ΔRR/ΔHR relationships after the VCP and in the V˙(E)/HR and RR/HR absolute values at VCP., Conclusions: In healthy young males, the ΔV˙E/ΔHR and ΔRR/ΔHR relationships during T and C incremental exercises can be reliably used to detect the VCP as an alternative to the ventilatory equivalent method.

In patients affected by chronic obstructive pulmonary disease (COPD), cardiopulmonary response to exercise was never related to the severity of emphysema (E) measured by high resolution computed tomography (HRCT). Sixteen patients (age=65±8 yrs; FEV(1)=54±18%pred; RV=160±28%pred) with moderate to severe E (quantified by lung HRCT as % voxels <-910 HU) were exercised on a cycle-ergometer to exhaustion. Oxygen uptake (V˙(O2)), carbon dioxide output (V˙(CO2)), ventilation (V˙(E)), tidal volume (V(T)), and end-tidal P(CO2) (PET(CO2)) derived variables were measured breath-by-breath. The % of E correlated with: (1) the ratio V(Tpeak) (r=0.74; p=0.001); (2) the V˙(E)/V˙(CO2) slope (r=-0.77; p=0.0004); (3) PET(CO2) values at peak exercise (r=0.80; p=0.0001). Also, the %E was strongly predicted by the following exercise equation: %E(EST) = 58.1 + 11.9 × ΔV˙(E)/V˙(CO2) (r=0.94; p<0.0001). A V(Tpeak)/FEV1 ratio>1 is typically observed in severe E patients; furthermore, the V˙(E)/V˙(CO2) slope and the PET(CO2peak) values decrease and increase respectively as more as the emphysema is severe., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The presence of obesity in COPD appears not to be a disadvantage with respect to dyspnea and weight-supported cycle exercise performance. We hypothesized that one explanation for this might be that the volume-reducing effects of obesity convey mechanical and respiratory muscle function advantages. Twelve obese chronic obstructive pulmonary disease (COPD) (OB) [forced expiratory volume in 1 s (FEV(1)) = 60%predicted; body mass index (BMI) = 32 ± 1 kg/m(2); mean ± SD] and 12 age-matched, normal-weight COPD (NW) (FEV(1) = 59%predicted; BMI = 23 ± 2 kg/m(2)) subjects were compared at rest and during symptom-limited constant-work-rate exercise at 75% of their maximum. Measurements included pulmonary function tests, operating lung volumes, esophageal pressure, and gastric pressure. OB vs. NW had a reduced total lung capacity (109 vs. 124%predicted; P < 0.05) and resting end-expiratory lung volume (130 vs. 158%predicted; P < 0.05). At rest, there was no difference in respiratory muscle strength but OB had greater (P < 0.05) static recoil and intra-abdominal pressures than NW. Peak ventilation, oxygen consumption, and exercise endurance times were similar in OB and NW. Pulmonary resistance fell (P < 0.05) at the onset of exercise in OB but not in NW. Resting inspiratory capacity, dyspnea/ventilation plots, and the ratio of respiratory muscle effort to tidal volume displacement were similar, as was the dynamic performance of the respiratory muscles including the diaphragm. In conclusion, the lack of increase in dyspnea and exercise intolerance in OB vs. NW could not be attributed to improvement in respiratory muscle function. Potential contributory factors included alterations in the elastic properties of the lungs, raised intra-abdominal pressures, reduced lung hyperinflation, and preserved inspiratory capacity.

Despite the growing evidence supporting the use of biventricular cardiac resynchronization therapy (CRT) in patients with chronic heart failure (CHF), the mechanisms whereby acute hemodynamic improvements lead to improved exertional dyspnea are not precisely known. We hypothesized that improved cardiac function and ventilation-perfusion relations following CRT would reduce ventilatory demand, thereby improving dynamic operating lung volumes and enhancing tidal volume expansion during exercise. This, in turn, would be expected to reduce perceived exertional dyspnea and contribute to improved exercise performance. In a randomized, double-blind, crossover study, we compared cardiovascular, metabolic, ventilatory responses (breathing pattern, operating lung volumes, pulmonary gas exchange) and exertional symptoms in seven stable CHF patients who undertook incremental cardiopulmonary cycle exercise test with CRT switched to the "on" (CRT(on)) or "off" (CRT(off)) modality. Following CRT(on), peak oxygen uptake was significantly increased by 15%, and dyspnea ratings were lower for a given work rate (at work rate of 40 W, dyspnea = 1 +/- 0.4 vs. 2.5 +/- 0.9 Borg units, P < 0.05) and ventilation (at ventilation of 31 l/min, dyspnea = 2 +/- 0.7 vs. 3.3 +/- 1.1 Borg units, P < 0.05). CRT(on) was associated with improvements in ventilatory threshold, oxygen pulse, and oxygen uptake/work rate relationships (10.2 +/- 1 vs. 7.9 +/- 1.3 ml.min(-1).W(-1), P < 0.05). CRT(on) reduced the ventilatory requirement during exercise as well as the steepness of ventilation-CO(2) production slope (35 +/- 4 vs. 45 +/- 7, P < 0.05). Changes in end-expiratory lung volume during exercise were less with CRT(on) than with CRT(off) (0.12 vs. 0.37 liter, P < 0.05), and breathing pattern was correspondingly slower and deeper. Biventricular pacing improved all noninvasive indexes of cardiac function and oxygen delivery during exercise. The decreased ventilatory demand, improved dynamic operating lung volumes, and the increased ability to expand tidal volume during exercise are potential factors in the reduction of exertional dyspnea.

The prevalence of activity-related breathlessness increases with age, particularly in women, but the specific underlying mechanisms have not been studied. This novel cross-sectional study was undertaken to examine the effects of age and sex, and their interaction, on the perceptual and ventilatory responses to incremental treadmill exercise in 73 healthy participants (age range 40-80 yr old) with normal pulmonary function. Age-related changes at a standardized oxygen uptake (Vo(2)) during exercise included significant increases in breathlessness ratings (Borg scale), ventilation (Ve), ventilatory equivalent for carbon dioxide, and the ratio of tidal volume (Vt) to dynamic inspiratory capacity (IC) (all P < 0.05). These changes were quantitatively similar in women (n = 39) and in men (n = 34). For the group as a whole, exertional breathlessness ratings increased as resting static inspiratory muscle strength diminished (P = 0.05), as exercise ventilation increased relative to capacity (P = 0.013) and as the Vt/IC ratio increased (P = 0.003) during exercise. Older women (60-80 yr old, n = 23) reported greater (P < 0.05) intensity of exertional breathlessness at a standardized Vo(2) and Ve than age-matched men (n = 16), despite similar age-related changes in ventilatory demand and dynamic ventilatory mechanics. These increases in breathlessness ratings in older women disappeared when sex differences in baseline maximal ventilatory capacity were accounted for. In conclusion, although increased exertional breathlessness with advancing age is multifactorial, contributory factors included higher ventilatory requirements during exercise, progressive inspiratory muscle weakness, and restrictive mechanical constraints on Vt expansion related to reduced IC. The sensory consequences of this age-related respiratory impairment were more pronounced in women, who, by nature, have relatively reduced maximal ventilatory reserve.

Rationale: Smokers with a relatively preserved FEV(1) may experience dyspnea and activity limitation but little is known about underlying mechanisms., Objectives: To examine ventilatory constraints during exercise in symptomatic smokers with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage I chronic obstructive lung disease (COPD) so as to uncover potential mechanisms of dyspnea and exercise curtailment., Methods: We compared resting pulmonary function and ventilatory responses (breathing pattern, operating lung volumes, pulmonary gas exchange) with incremental cycle exercise as well as Borg scale ratings of dyspnea intensity in 21 patients (post-bronchodilator FEV(1), 91 +/- 7% predicted, and FEV(1)/FVC, 60 +/- 6%; mean +/- SD) with significant breathlessness and 21 healthy age- and sex-matched control subjects with normal spirometry., Measurements and Main Results: In patients with COPD compared with control subjects, peak oxygen consumption and power output were significantly reduced by more than 20% and dyspnea ratings were higher for a given work rate and ventilation (P < 0.05). Compared with the control group, the COPD group had evidence of extensive small airway dysfunction with increased ventilatory requirements during exercise, likely on the basis of greater ventilation/perfusion abnormalities. Changes in end-expiratory lung volume during exercise were greater in COPD than in health (0.54 +/- 0.34 vs. 0.06 +/- 0.32 L, respectively; P < 0.05) and breathing pattern was correspondingly more shallow and rapid. Across groups, dyspnea intensity increased as ventilation expressed as a percentage of capacity increased (P < 0.0005) and as inspiratory reserve volume decreased (P < 0.0005)., Conclusions: Exertional dyspnea in symptomatic patients with mild COPD is associated with the combined deleterious effects of higher ventilatory demand and abnormal dynamic ventilatory mechanics, both of which are potentially amenable to treatment.

Expiratory muscle loading results in increased perception of respiratory effort; this response is mediated by non-vagal reflexes originating in the chest wall. Furosemide, due to its vagal effect, might not affect the perception of respiratory effort during expiratory flow-limited incremental exercise. In this study, we compared in nine healthy subjects the following determinants of exercise performance such as respiratory effort (Borg), workload (W'), ventilation (V'E), tidal volume (VT), respiratory frequency (f), and mean inspiratory flow (VT/TI), an index of central respiratory drive, during either standard incremental cycling exercise, or expiratory flow-limited incremental exercise. In addition we examined the effect of inhaled placebo, furosemide (40 or 80 mg) on the perception of respiratory effort following standard incremental cycling exercise and expiratory flow-limited incremental exercise. Compared with standard incremental cycling exercise, expiratory flow-limited incremental exercise increased the Borg score and VT/Ti, and decreased W',V'E ,VT, and f in all subjects at iso-workload. Neither placebo nor furosemide modified peak ventilatory variables, slopes, or intercepts of the relationships of the Borg score with W', V'E, VT/TI and VT during expiratory flow-limited incremental exercise. We conclude that (a) compared with standard incremental exercise, expiratory flow limited exercise increases central respiratory drive and perception of respiratory effort, and (b) furosemide does not affect the sensation of respiratory effort under the present conditions of increased drive to the respiratory muscles.

Dyspnea (respiratory difficulty) and activity limitation are the primary symptoms of chronic obstructive pulmonary disease (COPD) and progress relentlessly as the disease advances, contributing to reduced quality of life. In COPD, the mechanisms of dyspnea are multifactorial, but abnormal dynamic ventilatory mechanics are believed to play a central role. In flow-limited patients with COPD, dynamic lung hyperinflation (DH) occurs during exercise and has serious sensory and mechanical consequences. In several studies, indices of DH strongly correlate with ratings of dyspnea intensity during exercise, and strategies that reduce resting hyperinflation (either pharmacological or surgical) consistently result in reduced exertional dyspnea. The mechanisms by which DH gives rise to exertional dyspnea and exercise intolerance are complex, but recent mechanistic studies suggest that DH-induced inspiratory muscle loading, restriction of tidal volume expansion during exercise, and consequent neuromechanical uncoupling of the respiratory system are key components. This review examines the specific derangements of ventilatory mechanics that occur in COPD during exercise and attempts to provide a mechanistic rationale for the attendant respiratory discomfort and activity limitation.

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

The main purpose of this study was to examine the relative contribution of respiratory mechanical factors and the increased metabolic cost of locomotion to exertional breathlessness in obese women. We examined the relationship of intensity of breathlessness to ventilation (VE) when exertional oxygen uptake (VO2) of obesity was minimized by cycle exercise. Eighteen middle-aged (54+/-8 yr, mean+/-SD) obese [body mass index (BMI) 40.2+/-7.8 kg/m2] and 13 age-matched normal-weight (BMI 23.3+/-1.7 kg/m2) women were studied. Breathlessness at higher submaximal cycle work rates was significantly increased (by>or=1 Borg unit) in obese compared with normal-weight women, in association with a 35-45% increase in Ve and a higher metabolic cost of exercise. Obese women demonstrated greater resting expiratory flow limitation, reduced resting end-expiratory lung volume (EELV)(by 20%), and progressive increases in dynamic EELV during exercise: peak inspiratory capacity (IC) decreased by 16% (0.39 liter) of the resting value. VE/VO2 slopes were unchanged in obesity. Breathlessness ratings at any given VE or VO2 were not increased in obesity, suggesting that respiratory mechanical factors were not contributory. Our results indicate that in obese women, recruitment of resting IC and dynamic increases in EELV with exercise served to optimize operating lung volumes and to attenuate expiratory flow limitation so as to accommodate the increased ventilatory demand without increased breathlessness.

Lung hyperinflation commonly accompanies expiratory flow-limitation in patients with Chronic Obstructive Pulmonary Disease (COPD) and contributes importantly to dyspnea and activity limitation. It is not surprising, therefore, that lung hyperinflation has become an important therapeutic target in symptomatic COPD patients. There is increasing evidence that acute dynamic increases in lung hyperinflation, under conditions of worsening expiratory flow-limitation and increased ventilatory demand (or both) can seriously stress cardiopulmonary reserves, particularly in patients with more advanced disease. Our understanding of the physiological mechanisms of dynamic lung hyperinflation during both physical activity and exacerbations in COPD continues to grow, together with an appreciation of its serious negative mechanical and sensory consequences. In this review, we will discuss the basic pathophysiology of COPD during rest, exercise and exacerbation so as to better understand how this can be pharmacologically manipulated for the patient's benefit. Finally, we will review current concepts of the mechanisms of symptom relief and improved exercise endurance following pharmacological lung volume reduction.

Introduction: Length-tension and force-velocity characteristics of respiratory muscles and hyperinflation are the likely determinants of dyspnea in subjects exercising under hyperbaric conditions. We hypothesize that hyperinflation plays a minor role and that the reduced velocity of shortening of the respiratory muscles modulates dyspnea for any given pleural pressure., Methods: We studied five normal subjects who performed an incremental exercise test on a cycloergometer in both normobaric (SL) and hyperbaric (4 ATA) conditions. We measured breathing pattern, inspiratory pleural pressure swing (Pessw), Delta Pes (i.e., the difference between the most and the less negative pleural pressures during tidal breathing), and dyspnea intensity (Borg score). End-expiratory lung volume (EELV) changes were evaluated by measuring changes in inspiratory capacity. Mean inspiratory flow (VT/TI) was used as an index of velocity of shortening of respiratory muscles., Results: Compared with SL, at 4 ATA, peak exercise ventilation (VE) (84.5 vs 62.2 L x min(-1)) and VT/TI (2.99 vs 2.16 L x s)(-1) were lower, Pessw (30.9 vs 38.6 cm H2O) and Delta Pes (43.8 vs 62.2 cm H2O) were higher, and Borg score was not different (7.60 vs 8.20 au). EELV decreased progressively during exercise but remained higher than at SL. Borg score was greater for a same VE and lower for a same Delta Pes. VT/TI was lower for a same Pessw. The differences in EELV between SL and 4 ATA did not relate with the concurrent changes in Borg score., Conclusion: The results confirm our hypothesis that during exercise in hyperbaric conditions, decreased velocity of shortening of respiratory muscles modulates pressure-induced increases in dyspnea, with hyperinflation playing a minor role.