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In heart failure (HF), exertional dyspnea is a common symptom, but validated field-based tests for its measurement are limited. The Dyspnea Challenge is a two-minute uphill treadmill walk designed to measure exertional dyspnea in cardiopulmonary disease.The purpose of this study was to establish the test-retest reliability of the Dyspnea Challenge in HF and to compare the exercise responses to a group with chronic obstructive pulmonary disease (COPD).The study was an experimental, single-blind, randomized, multi-site project that recruited individuals with HF (New York Heart Association I-III) and COPD (Global Initiative for Chronic Obstructive Lung Disease II-IV). Participants completed two visits. On the first visit, participants performed two six-minute walk tests (6MWT), followed by two to three Dyspnea Challenges to calculate treadmill speed and gradient. At Visit Two, participants performed two separate Dyspnea Challenges, with one including measures of pulmonary gas exchange and central hemodynamics.Twenty-one individuals with HF (10 female; 66±11years; ejection fraction:45.3 ± 6.1%; six-minute distance(6MWD) 520 ± 97 m), and 25 COPD (11 female; 68 ± 10 yr; forced expiratory volume in 1 s:47.6 ± 11.5%; 6MWD: 430 ± 101 m). Intraclass correlation coefficients demonstrated excellent test-retest reliability for HF (0.94, P.01) and COPD (0.95, P.01). While achieving similar end-exercise exertional dyspnea intensities (P=.60), the HF group walked at a higher average speed (4.2 ± 0.8 vs. 3.5 ± 0.8km·hThe Dyspnea Challenge is a reliable test-retest measure of exertional dyspnea in HF. Typical to their pathologies, HF seemed limited by an inadequate modulation of cardiac output, while ventilatory constraints hampered those with COPD.

The traditional Pentecostal understanding of the events of Acts 8.4-25 typically centers upon a two-stage model for the reception of the Spirit. While this article does not seek to preclude the plausibility of such a model, it does, however, seek to take a step further by providing a culturally-sensitive analysis concerning how the coming of the Spirit, the apostolic imposition of hands (Acts 8.17), and the concept of worship in ‘spirit and truth’ (Jn 4.24) serves as a paradigm for ethnic reconciliation.

The Dyspnoea Challenge has been developed to facilitate the field-based measure of exertional dyspnoea(ED). To further validate the test, we aimed to; investigate the relationship between end-exercise ED, generated by a fixed-intensity Dyspnoea Challenge(DCThirty-two individuals (15 female) with COPD (GOLD II-IV) (age: 69.7 ± 9.4 yrs; FEVEnd-exercise ED measured during the DCThe Dyspnoea Challenge is correlated to different parameters of disease severity and produces a similar physiological and ED response to that of the 6MWT with the added benefit of being appropriate for longitudinal assessment of ED.

The Dyspnoea Challenge is a two-minute treadmill walk designed to measure exertional dyspnoea(ED). To efficiently individualise workload, we aimed to assess; 1) whether the Dyspnoea Challenge is responsive to 1% changes in treadmill gradient and 2) the minimum gradient variation necessary to generate a clinically meaningful change in ED (≥1 modified Borg scale).Thirty individuals with COPD(GOLD II-IV) (age: 69.2 ± 9.2 years; FEVHigher treadmill gradients generated stronger intensities of ED (3%:2.6 ± 1.8; 4%:2.8 ± 2.2; 5%:3.2 ± 2.2; 6%:3.4 ± 2.2; 7%:3.7 ± 1.8; 8%:4.0 ± 2.1units). Statistical changes were observed in ED(e.g.,3 vs. 5%: P = .03) and the MDP discomfort data(e.g.,4 vs. 6%: P = .04) at ≥ a 2% variation in treadmill gradient. Linear regression found a 4% variation in treadmill gradient corresponded to a rise in ED ≥ 1unit. Increases in ED intensity corresponded to heightened sensations of work/effort(P .01) and breathing frequency(P .01). There were no changes in emotional constructs(P = .27). While there was an increase in HR with increasing gradient(P .01), no differences were observed in end-exercise STo significantly change ED, the treadmill gradient must be manipulated by ≥ 2%, with a ≥ 4% change in gradient required to induce a clinically meaningful change in ED.

BACKGROUND: Exercise stress testing (EST) in patients with poor functional capacity measured by time on treadmill is typically deemed inconclusive and usually leads to further downstream testing. The aim of this study was firstly to evaluate the maximum rate pressure product (MRPP) during initial EST to assessthe need for follow-up testing; and secondly to investigate if MRPP is better than age predicted maximum heart rate (APMHR) for diagnostic outcome based on follow up cardiovascular (CV) events in patients with inconclusive EST due to poor functional capacity. METHODS: From a total of 2761 tests performed, 236 tests were considered inconclusive due to poor functional capacity which were available for analysis. From receiver operating characteristic (ROC) analysis, a cut-off value for MRPP of 25000 was chosen using CV events as the outcome measure (sensitivity 97%, specificity 45%). Cases were then categorised into those with an MRPP > 25000 and < 25000. RESULTS: Regardless of treadmill time, any patient attaining an MRPP > 25000 had no abnormal downstream testing or CV events at 2 years follow-up. On ROC analysis MRPP outperformed APMHR for sensitivity and specificity (area under curve 0.76 vs. 0.59, respectively). CONCLUSIONS: The results suggest that regardless of functional capacity, individuals whose EST is terminated at maximal fatigue, with no electrocardiogram evidence or symptoms of myocardial ischemia and yields an MRPP > 25000, do not require further downstream testing. Furthermore, this group of patients, while not immune to future CV events, have significantly better outcomes than those not attaining a MRPP > 25000.

We examined the interactions between acoustically driven mood modulation and dyspnoea. Following familiarisation, 18 healthy participants attended three experimental sessions on separate days performing two 5 min treadmill tests with a 30 min interval per session while listening to either a positive, negative or neutral set of standardised International Affective Digitised Sounds (IADS). Participants rated intensity and affective domains of dyspnoea during the first exercise test and mood during the second. Mood valence was significantly higher when listening to positive (mean (95% CI): 6.5 (5.9–7.2)) compared with negative sounds (3.6 (2.9–4.4); pintensity and affect were statistically significantly lower when listening to positive (2.4 (1.8–2.9) and 1.3 (0.7–1.9)) compared with negative IADS (3.2 (2.3–3.7), p=0.013 and 2.3 (1.3–3.3), p=0.009). These findings indicate that acoustically induced mood changes influence exertional dyspnoea.

Chest wall strapping has been used to assess mechanisms of dyspnea with restrictive lung disease. This study examined the hypothesis that dyspnea with restriction depends principally on the degree of reflex ventilatory stimulation. We compared dyspnea at the same (iso)ventilation when added dead space provided a component of the ventilatory stimulus during exercise. Eleven healthy men undertook a randomized controlled crossover trial that compared four constant work exercise conditions: 1) control (CTRL): unrestricted breathing at 90% gas exchange threshold (GET); 2) CTRL+dead space (DS): unrestricted breathing with 0.6-l dead space, at isoventilation to CTRL due to reduced exercise intensity; 3) CWS: chest wall strapping at 90% GET; and 4) CWS+DS: chest strapping with 0.6-l dead space, at isoventilation to CWS with reduced exercise intensity. Chest strapping reduced forced vital capacity by 30.4 ± 2.2% (mean ± SE). Dyspnea at isoventilation was unchanged with CTRL+DS compared with CTRL (1.93 ± 0.49 and 2.17 ± 0.43, 0–10 numeric rating scale, respectively; P = 0.244). Dyspnea was lower with CWS+DS compared with CWS (3.40 ± 0.52 and 4.51 ± 0.53, respectively; P = 0.003). Perceived leg fatigue was reduced with CTRL+DS compared with CTRL (2.36 ± 0.48 and 2.86 ± 0.59, respectively; P = 0.049) and lower with CWS+DS compared with CWS (1.86 ± 0.30 and 4.00 ± 0.79, respectively; P = 0.006). With unrestricted breathing, dead space did not change dyspnea at isoventilation, suggesting that dyspnea does not depend on the mode of reflex ventilatory stimulation in healthy individuals. With chest strapping, dead space presented a less potent stimulus to dyspnea, raising the possibility that leg muscle work contributes to dyspnea perception independent of the ventilatory stimulus. NEW & NOTEWORTHY Chest wall strapping was applied to healthy humans to simulate restrictive lung disease. With chest wall strapping, dyspnea was reduced when dead space substituted for part of a constant exercise stimulus to ventilation. Dyspnea associated with chest wall strapping depended on the contribution of leg muscle work to ventilatory stimulation. Chest wall strapping might not be a clinically relevant model to determine whether an alternative reflex ventilatory stimulus mimics the intensity of exertional dyspnea.

Background: Dobutamine stress echocardiography (DSE) is a commonly used diagnostic stress test for the assessment of various cardiac pathologies on patients unable to perform exercise. Unlike exercise, there is no reliable subjective termination end-point such as fatigue to rely on. Consequently, DSE’s are often concluded at a predetermined age predicted maximal heart rate (APMHR) such as 85%. The aim of this study was to assess if APMHR, heart rate reserve (HRR) and the maximum rate pressure product (MRPP) are valid measures of future cardiovascular (CV) events in otherwise negative DSEs. Methods: Following exclusions, receiver operating curve (ROC) analyses were performed on 652 patients using CV events during the follow-up period (4.2 ± 1.8 years) as the outcome variable. Results: ROC analyses failed to produce a statistically valid model for MRPP (p =.227, area under curve (AUC)=0.55) with a sensitivity and specificity of 21.1% and 91.9%, respectively at the optimal cut point (14948 MRPP). To the contrary, APMHR produced a sensitivity and specificity of 74.7% and 60.9%, respectively (p

Exercise stress echocardiograms (ESEs) are a functional cardiovascular (CV) test typically used for the investigation of coronary artery disease. ESEs are often terminated at a predetermined age-predicted maximum heart rate (APMHR) to facilitate timely acquisition of ultrasound images at peak exercise. Although an APMHR of 85% is often used, this has not been validated as a suitable termination end point. Heart rate blood pressure product (HRBPP) as an established measure of myocardial work may provide a more reliable assessment of cardiac workload. The aim of this study was to assess maximal HRBPP (MHRBPP) and APMHR as markers of cardiac workload during ESE, using CV events at mean follow-up as the outcome variable. After exclusions, 712 patients being investigated for ischemic heart disease, performed an ESE to volitional fatigue using the standard Bruce protocol. Patient demographics and test data were collected and patients followed for 4.4 ± 2.1 years. Cut-points for MHRBPP (25,060; area under curve 0.77) and APMHR (93.8% and 97.9%; area under curve 0.71; p = 0.12 for difference) were established from receiver operating characteristic analysis. Those achieving an APMHR85% but MHRBPP25,060 had significantly more CV events than achieving an MHRBPP25,060 regardless of APMHR (p0.05). In conclusion, the current study demonstrates the superior prognostic power of MHRBPP over APMHR alone for the prediction of future CV events in patients performing an otherwise negative ESE for the detection of myocardial ischemia.

Most of the current guidelines for pulmonary rehabilitation recommend higher, over lower, intensity exercise training for COPD. Typically, we consider intensity of exercise training to be a key component of any exercise training programme. Whilst studies of young individuals have demonstrated that higher exercise training intensity results in greater improvements in exercise capacity, the evidence for older patients is not so clear cut. In COPD, there is limited evidence regarding the optimal intensity of exercise training. Using both physiological (peak exercise capacity) and patient-centred (e.g. quality of life) outcomes, it remains inconclusive if higher intensity exercise training bestows any greater benefit than low-intensity exercise. If we examine the data from interval training studies, which used both high- and low-intensity interval and continuous exercise, we are able to generate more data for comparison. Unfortunately, these data are challenging to interpret due to heterogeneity in how interval training was prescribed. However, when we normalize the interval training data for training volume and examine the change in peak cycling power, there is a relationship between training intensity and increase in peak power (Wpeak, r = 0.68, P

Background and objectiveThe mechanism of dyspnoea associated with pleural effusion is uncertain. A cohort of patients requiring thoracoscopy for unilateral exudative effusion were investigated for associations between dyspnoea and suggested predictors: impaired ipsilateral diaphragm movement, effusion volume and restricted lung inflation.MethodsBaseline Dyspnoea Index, respiratory function, and ultrasound assessment of ipsilateral diaphragm movement were assessed prior to thoracoscopy, when effusion volume was measured. Transitional Dyspnoea Index (change from baseline) was assessed 4 and 8 weeks after thoracoscopy. Pearson product moment assessed bivariate correlations and a general linear model examined how well total lung capacity (measuring restricted lung inflation), effusion volume and impaired diaphragm movement predicted Baseline Dyspnoea Index. Un-paired t tests compared the groups with normal and impaired diaphragm movement.Results19 patients were studied (14 malignant etiology). Total lung capacity was associated with Baseline Dyspnoea Index (r = 0.68, P = 0.003). Effusion volume (r = -0.138, P = 0.60) and diaphragm movement (P = 0.09) were not associated with Baseline Dyspnoea Index. Effusion volume was larger with impaired diaphragm movement compared to normal diaphragm movement (2.16 +/- SD 0.95 vs.1.16 +/- 0.92 L, P = 0.009). Total lung capacity was lower with impaired diaphragm movement compared to normal diaphragm movement (65.4 +/- 10.3 vs 78.2 +/- 8.6% predicted, P = 0.011). The optimal general linear model to predict Baseline Dyspnoea Index used total lung capacity alone (adjusted R-2 = 0.42, P = 0.003). In nine participants with controlled effusion, baseline effusion volume (r = 0.775, P = 0.014) and total lung capacity (r = -0.690, P = 0.040) were associated with Transitional Dyspnoea Index.ConclusionsRestricted lung inflation was the principal predictor of increased dyspnoea prior to thoracoscopic drainage of effusion, with no independent additional association with either effusion volume or impaired ipsilateral diaphragm movement. Restricted lung inflation may be an important determinant of the dyspnoea associated with pleural effusion.

Objective: Exercise treadmill testing (ETT) is a well-established procedure for the diagnosis, prognosis and functional assessment of patients with suspected cardiovascular disease. The use of handrail support during ETT is often discouraged as this has been demonstrated to overestimate functional capacity. It is unknown if this increase in functional capacity translates to an increase in cardiac workload. The aim of this study was to investigate if the use of handrail support during maximal ETT produces an increase in cardiac workload when compared to no handrail support. Approach: Fifty-two consenting volunteers performed two maximal ETTs, one with handrail support and the other without, approximately one week apart. Participants were identified as either experienced treadmill users (treadmill use >= once per fortnight) (n = 24) or inexperienced users (n = 28). Cardiac workload was quantified using rate pressure product (RPP) (systolic blood pressure (SBP) x heart rate (HR)) Main results: The average age of participants was 38.4 +/- 11.4 years (44% male). Overall exercise duration was significantly prolonged by 44.4% with handrail support (with support 15:01 +/- 2:54 min; without support 10:24 +/- 2:09 min). Overall HR, SBP and maximum RPP were not significantly different between conditions. For the 28 inexperienced treadmill users maximum RPP was significantly higher during handrail support (7.5% increase) (with support 34 417 +/- 4906; without support 31 821 +/- 4565). Significance: Handrail support overestimates functional capacity, however produces greater maximal RPP in inexperienced treadmill users. If accurate aerobic data is required during ETT, or subjects performing ETT are experienced treadmill users, handrail support should be discouraged. Non-treadmill users or subjects fearful of falling may benefit from handrail support, particularly when maximal cardiac workload is desired.

AB PURPOSE: To test the reliability of Timed Up and Go Tests (TUGTs) in cardiac rehabilitation (CR) and compare TUGTs to the 6-Minute Walk Test (6MWT) for outcome measurement. METHODS: Sixty-one of 154 consecutive community-based CR patients were prospectively recruited. Subjects undertook repeated TUGTs and 6MWTs at the start of CR (start-CR), postdischarge from CR (post-CR), and 6 months postdischarge from CR (6 months post-CR). The main outcome measurements were TUGT time (TUGTT) and 6MWT distance (6MWD). RESULTS: Mean (SD) TUGTT1 and TUGTT2 at the 3 assessments were 6.29 (1.30) and 5.94 (1.20); 5.81 (1.22) and 5.53 (1.09); and 5.39 (1.60) and 5.01 (1.28) seconds, respectively. A reduction in TUGTT occurred between each outcome point (P

Most of the current guidelines for pulmonary rehabilitation recommend higher, over lower, intensity exercise training for COPD. Typically, we consider intensity of exercise training to be a key component of any exercise training programme. Whilst studies of young individuals have demonstrated that higher exercise training intensity results in greater improvements in exercise capacity, the evidence for older patients is not so clear cut. In COPD, there is limited evidence regarding the optimal intensity of exercise training. Using both physiological (peak exercise capacity) and patient-centred (e.g. quality of life) outcomes, it remains inconclusive if higher intensity exercise training bestows any greater benefit than low-intensity exercise. If we examine the data from interval training studies, which used both high- and low-intensity interval and continuous exercise, we are able to generate more data for comparison. Unfortunately, these data are challenging to interpret due to heterogeneity in how interval training was prescribed. However, when we normalize the interval training data for training volume and examine the change in peak cycling power, there is a relationship between training intensity and increase in peak power (Wpeak , r = 0.68, P 0.05). Hence, whilst there is an inconclusive amount of evidence to support this intervention based on studies that only examined high- versus low-intensity continuous exercise, the additional data from interval training studies would suggest that higher intensity may be superior in terms of increases in Wpeak . Future studies should focus on establishing a threshold and an optimal training intensity for COPD.

The 6-minute walk test (6MWT) is a common outcome measurement in cardiac rehabilitation. However, a search of the literature found no established guidelines for use of the 6MWT in cardiac rehabilitation.Systematic review of the validity, reliability and responsiveness of the 6MWT in cardiac rehabilitation.OvidMEDLINE, SPORTdiscus, EMBASE, CINAHL, Cochrane Reviews and Cochrane Clinical Trials between January 1948 and April 2011.Studies using 6MWTs in subjects with coronary artery disease undergoing cardiac rehabilitation on an outpatient basis, published in English, were included. STUDY APPRAISAL AND METHODS: Quantitative and qualitative analyses were conducted, including quality assessment of methodology, meta-analysis and assessment against level of evidence criteria.Fifteen articles met the inclusion criteria. One high-quality study was identified for reliability, six high-quality studies were identified for validity and 11 high-quality studies were identified for responsiveness. The meta-analysis found strong evidence that the 6MWT was responsive to change in clinical status following cardiac rehabilitation, with an estimated mean difference in 6-minute walk distance of 60.43m (95% confidence interval 54.57 to 66.30m; P0.001). Qualitative analysis indicated moderate evidence for repeatability of the 6MWT in patients undergoing cardiac rehabilitation, for a 2% to 8% learning effect between repeated 6MWTs, for a relationship between peak heart rate during the 6MWT and during cycle exercise at the ventilatory threshold, and for moderate-to-high correlation between the 6-minute walk distance and maximum metabolic equivalents achieved on symptom-limited exercise tests.Few studies assessed similar aspects of validity for the 6MWT.Strong evidence suggests that the 6MWT is responsive to clinical change following cardiac rehabilitation. Intra- and intertester reliability of the 6MWT and its validity in patients undergoing cardiac rehabilitation requires further research.

OBJECTIVES: The purpose of this study was to compare the effectiveness of moderate-intensity stationary cycling and walking exercise programmes in the early postoperative period after first-time coronary artery bypass graft surgery. METHODS: In this prospective trial, 64 patients (57 men, 7 women, mean age = 66 ± 9 years) performed twice daily, moderate-intensity exercise sessions, of 10-min duration, from postoperative day 3 until discharge from hospital. Patients were randomly assigned to stationary cycling or walking exercise intervention groups. Preoperative and discharge functional exercise capacity and health-related quality of life were assessed using 6-min walk and cycle assessments and the SF-36 version 2.0 questionnaire. Compliance with exercise was calculated as the proportion of scheduled exercise sessions completed. RESULTS: There were no significant differences between intervention groups at hospital discharge for 6-min walk distance (cyclists: 402 ± 93 m vs walkers: 417 ± 86 m, P= 0.803), 6-min cycle work (cyclists: 15.0 ± 6.4 kJ vs walkers: 14.0 ± 6.3 kJ, P= 0.798) or healthrelated quality of life. There was no significant difference between intervention groups for postoperative length of hospital stay (P= 0.335). Compliance rates for intervention groups were cyclists: 185/246 (75%) scheduled exercise sessions completed vs walkers: 199/242 (82%) scheduled exercise sessions completed (P= 0.162). CONCLUSIONS: Stationary cycling provides a well-tolerated and clinically effective alternative to walking in the early postoperative period after coronary artery bypass graft surgery. The optimal frequency, intensity and duration of exercise in the early postoperative period require further investigation. (Clinical trials register: Australian New Zealand Clinical Trials Registry; identification number: ACTRN12608000359336; http://www.anzctr.org.au/trial_view.aspx?ID=82978).

Rationale: Opioids are commonly used to relieve dyspnea, but clinical data are mixed and practice varies widely. Objectives: Evaluate the effect of morphine on dyspnea and ventilatory drive under well-controlled laboratory conditions. Methods: Six healthy volunteers received morphine (0.07 mg/kg) and placebo intravenously on separate days (randomized, blinded). We measured two responses to a CO2 stimulus: (1) perceptual response (breathing discomfort; described by subjects as “air hunger”) induced by increasing partial pressure of end-tidal carbon dioxide (PetCO2) during restricted ventilation, measured with a visual analog scale (range, “neutral” to “intolerable”); and (2) ventilatory response, measured in separate trials during unrestricted breathing. Measurements and Main Results: We determined the PetCO2 that produced a 60% breathing discomfort rating in each subject before morphine (median, 8.5 mm Hg above resting PetCO2). At the same PetCO2 after morphine administration, median breathing discomfort was reduced by 65% of its pretreatment value; P < 0.001. Ventilation fell 28% at the same PetCO2; P < 0.01. The effect of morphine on breathing discomfort was not significantly correlated with the effect on ventilatory response. Placebo had no effect. Conclusions: (1) A moderate morphine dose produced substantial relief of laboratory dyspnea, with a smaller reduction of ventilation. (2) In contrast to an earlier laboratory model of breathing effort, this laboratory model of air hunger established a highly significant treatment effect consistent in magnitude with clinical studies of opioids. Laboratory studies require fewer subjects and enable physiological measurements that are difficult to make in a clinical setting. Within-subject comparison of the response to carefully controlled laboratory stimuli can be an efficient means to optimize treatments before clinical trials.

PURPOSE: Home-based and center-based cardiac rehabilitation (CR) have demonstrated similar levels of risk factor reduction. Cardiac rehabilitation models with fewer exercise sessions may be as effective as traditional models. This study reviewed a community phase II CR database from 2007 to 2010. METHODS: A fast-track CR (FTCR) group was introduced alongside an existing traditional CR (TCR) program. The 2 programs ran concurrently on different days. Both FTCR and TCR treatment groups undertook supervised low to moderate intensity exercise training for 6 weeks and were provided with home exercise advice. Fast-track CR included once-weekly exercise sessions and a 1-time 7-hour education session; TCR included twice-weekly exercise and education sessions. Similar education was provided in both programs. Six-minute walk test distance (6MWD) was assessed pre-CR and post-CR for both groups. RESULTS: Six hundred and twenty patients enrolled in CR during the period, and patients elected or were assigned (not randomized) to FTCR (n = 197) or to TCR (n = 423) treatment groups. Complete 6MWD data sets were available for 115 FTCR and 254 TCR subjects. Repeated-measures analysis of variance found 6MWD outcomes to be similar for both groups over both assessments combined and at each assessment point. Improvements in 6MWD post-CR were different for men and women in the CR database (8% vs 5%, respectively, P < .001). CONCLUSIONS: Six-minute walk test distance outcomes were not different for subjects undergoing once-weekly or twice-weekly supervised CR exercise sessions. CR models with fewer supervised exercise sessions may provide similar functional outcomes to traditional CR models.

In many diseases across a range of pathologies (e.g., cardiopulmonary, neuromuscular, and cancer), chronic dyspnea, particularly on exertion, is a major debilitating symptom often associated with clinical anxiety/depression. This study aims to explore the interaction between mood state and exertional dyspnea in a healthy population. Following familiarization, 20 healthy subjects (27-54 years old) performed six 5-min treadmill tests on three separate days. On each day subjects viewed randomly assigned images designed to induce positive, negative, or neutral mood states (International Affective Picture System). For each condition, at minute intervals, subjects rated dyspnea (sensory and affective domains) in the first test and mood (valence and arousal domains) in the second test. Oxygen uptake (V̇o2, liters/min), carbon dioxide production (V̇co2, liters/min), ventilation (V̇e, liters/min), respiratory frequency (fR, beats/min), and heart rate (HR, bpm), were measured throughout the exercise. V̇o2, V̇co2, V̇e, HR, and fR were not statistically significantly different among the three mood states ( P > 0.05). Mood valence was significantly higher with parallel viewing of positive (last 2-min mean ± SE = 6.9 ± 0.2) compared with negative pictures (2.4 ± 0.2; P < 0.001). Both sensory and affective domains of dyspnea were significantly higher during negative (sensory: 5.6 ± 0.3; affective: 3.3 ± 0.5) compared with positive mood (sensory: 4.4 ± 0.4, P < 0.001; affective: 2.1 ± 0.4, P = 0.002). These findings suggest that positive mood alleviates both the sensory and affective domains of exertional dyspnea in healthy subjects. Thus the treatment of anxiety/depression in dyspenic populations could be a worthwhile therapeutic strategy in increasing symptom-limited exercise tolerance, thereby contributing to improved quality of life.

SummaryWe have examined the role of age on the continuous positive airway pressure (CPAP) levels required to treat two groups of elderly (n=70) and young (n=70) sleep apneic patients, matched for disease severity (apnea/hypopnea index), body mass index and neck circumference. Elderly patients required lower CPAP levels compared to young [mean (sd): 6.9(1.9)cm H2O and 9.4(3.5)cm H2O, respectively; P

Aims Breathlessness is a cardinal symptom of heart failure and the altered regulation of breathing is common. The contribution of abnormal central nervous system activity has not previously been investigated directly, although abnormal autonomic responses have been described. Our aim was to assess whether heart failure patients exhibit different patterns of regional brain activation after exercise stress. Methods We used positron emission tomography with (H2O)-O-15, to measure changes in regional cerebral blood flow (rCBF) and absolute global cerebral blood flow (gCBF) in 6 mate class II/III heart failure patients and 6 normal controls. Breathlessness (0-5 visual analogue scale) and respiratory parameters were measured at rest, after horizontal bicycle exercise and during isocapnic hyperventilation. CBF was measured in each condition in all subjects. Results Both groups were similarly breathless after exercise and the respiratory parameters were comparable. rCBF differences for the main comparison (exercise vs; hyperventilation) were: activation of the right frontal medial. gyrus (P < 0.001, Z = 4.90) and left precentral gyrus (P < 0.03, Z = 4.66) in controls but not in patients. Both groups had rCBF increases in the left anterior cingulate (P < 0.05, Z = 4.67) and right dorsal cingulate cortex (P < 0.05, Z = 4.66). The gCBF did not differ between exercise, isocapnic hyperventilation and rest in patients but, in controls, gCBF was greater after exercise compared to either isocapnic hyperventilation or rest. Conclusion Heart failure patients had a distinct pattern of regional cortical activity with exercise-induced breathlessness but unvarying CBF values between conditions. These central neural differences in activity may contribute to some features of heart failure, such as variability in symptoms and autonomic dysregulation. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.

Some patients with lung disease retain CO(2), while others with similar lung function do not. This could be explained if CO(2) retainers had a pre-existing low hypercapnic ventilatory response (HCVR) and, from this, a tendency to retain CO(2). To test if such a phenomenon exists in healthy people, we determined the change in end-tidal P(CO(2)) (deltaPET(CO(2))) produced by the addition of a dead-space (DS), during wakefulness and sleep, and related this to the HCVR measured awake. The group mean (n=14) HCVR slope was 2.2+/-1.1 (S.D.) L min(-1) mmHg(-1). The deltaPET(CO(2)) with the application of DS was 1.6+/-1.6 mmHg awake and 2.6+/-2.2 mmHg asleep. During wakefulness the deltaPET(CO(2)) with DS did not correlate with the HCVR slope. However, during sleep, four subjects had a marked increase in the deltaPET(CO(2)) (3.7, 4.3, 6.2, 8.0 mmHg) and a relatively low HCVR (slope 1.5, 1.7, 1.5, 1.7 L min(-1) mmHg(-1), respectively). We speculate that such individuals, should they develop lung disease, may be predisposed to retain CO(2).

In young people, a sleep-related reduction in the gain of the ventilatory chemoreflex feedback loop occurs; in the elderly, it has been reported that no sleep-related reduction occurs. A relatively high loop gain could contribute to periodic breathing and central sleep apnoea in the elderly. This study tested the hypothesis that ageing is associated with a reduction in the magnitude of the sleep-related decrease in the hypercapnic ventilatory response (HCVR). The HCVR was measured using a steady state method, awake and asleep, in groups (n = 10) of elderly (66-81 yrs) and young (23-35 yrs) nonapnoeics. Upper airway resistance was maintained close to wakefulness levels using continuous positive airway pressure (mean sleep-related increase in resistance: elderly 1.6 +/- 1.2 cmH2O L x s(-1), young 1.2 +/- 0.8 cmH2O x L x s(-1)). The sleep-related decrease in the HCVR was similar in the elderly and young groups (elderly: wake 0.14 +/- 0.06 and sleep 0.06 +/- 0.02 L min(-1) x kPa and young, wake 0.19 +/- 0.07 and sleep 0.10 +/- 0.04 L x min(-1) x kPa). Ageing per se was shown not to change the magnitude of the sleep-related decrease in hypercapnic ventilatory response. The authors speculate that age-related changes in the hypercapnic ventilatory response are unlikely to contribute to the increased prevalence of central sleep apnoea in the elderly.

Air hunger (uncomfortable urge to breathe) is a component of dyspnea (shortness of breath). Three human H215O positron emission tomography (PET) studies have identified activation of phylogenetically ancient structures in limbic and paralimbic regions during dyspnea. Other studies have shown activation of these structures during other sensations that alert the organism to urgent homeostatic imbalance: pain, thirst, and hunger for food. We employed blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine activation during air hunger. fMRI conferred several advantages over PET: enhanced signal-to-noise, greater spatial resolution, and lack of ionizing radiation, enabling a greater number of trials in each subject. Six healthy men and women were mechanically ventilated at 12–14 breaths/min. The primary experiment was conducted at mean end-tidal Pco2of 41 Torr. Moderate to severe air hunger was evoked during 42-s epochs of lower tidal volume (mean = 0.75 L). Subjects described the sensation as “like breath-hold,” “urge to breathe,” and “starved for air.” In the baseline condition, air hunger was consistently relieved by epochs of higher tidal volume (mean = 1.47 L). A control experiment in the same subjects under a background of mild hypocapnia (mean end-tidal PCO2= 33 Torr) employed similar tidal volumes but did not evoke air hunger, controlling for stimulus variables not related to dyspnea. During each experiment, we maintained constant end-tidal Pco2and PO2to avoid systematic changes in global cerebral blood flow. Whole-brain images were acquired every 5 s (T2*, 56 slices, voxel resolution 3 × 3 × 3 mm). Activations associated with air hunger were determined using voxel-based interaction analysis of covariance that compared data between primary and control experiments (SPM99). We detected activations not seen in the earlier PET study using a similar air hunger stimulus ( Banzett et al. 2000 ). Limbic and paralimbic loci activated in the present study were within anterior insula (seen in all 3 published studies of dyspnea), anterior cingulate, operculum, cerebellum, amygdala, thalamus, and basal ganglia. Elements of frontoparietal attentional networks were also identified. The consistency of anterior insular activation across subjects in this study and across published studies suggests that the insula is essential to dyspnea perception, although present data suggest that the insula acts in concert with a larger neural network.

We employed an associative learning paradigm to test the hypothesis that exercise hyperpnea in humans arises from learned responses forged by prior experience. Twelve subjects undertook a “conditioning” and a “nonconditioning” session on separate days, with order of performance counterbalanced among subjects. In both sessions, subjects performed repeated bouts of 6 min of treadmill exercise, each separated by 5 min of rest. The only difference between sessions was that all the second-to-penultimate runs of the conditioning session were performed with added dead space in the breathing circuit. Cardiorespiratory responses during the first and last runs (the “control” and “test” runs) were compared for each session. Steady-state exercise end-tidal Pco2was significantly lower ( P= 0.003) during test than during control runs for both sessions (dropping by 1.8 ± 2 and 1.4 ± 3 Torr during conditioning and nonconditioning sessions, respectively). This and all other test-control run differences tended to be greater during the first session performed regardless of session type. Our data provide no support for the hypothesis implicating associative learning processes in the ventilatory response to exercise in humans.

PURPOSE: The purpose of this study was twofold: (1) to determine whether exercise training adds to the benefit of a dyspnea self-management (DM) program; and (2) to determine if there is a “dose response” to supervised exercise training (0, 4, or 24 sessions) in dyspnea, exercise performance, and health-related quality of life. METHODS: Subjects with chronic obstructive pulmonary disease (n = 103, 46 men, 57 women; age 66 ± 8 years; forced expiratory volume in 1 second 44.8 ± 14% predicted) were randomized to DM, DM-exposure, or DM-training. Dyspnea self-management included individualized education about dyspnea management strategies, a home-walking prescription, and daily logs. Outcomes were measured at baseline and 2 months as part of a 1-year longitudinal randomized clinical trial. Outcomes included dyspnea during laboratory exercise and with activities of daily living (Chronic Respiratory Questionnaire [CRQ]), Shortness of Breath Questionnaire, Baseline/Transitional Dyspnea Index), exercise performance (incremental treadmill tests (ITTs) and endurance treadmill tests (ETTs), 6-minute walk (6MW), and health-related quality of life (SF-36). RESULTS: The DM-training group had significantly greater improvements than the DM-exposure and the DM groups in dyspnea at isotime during ITT (P = .006); exercise performance during ITT (P = .005), ETT (P = .003), and 6MW (P = .01); SF-36 Vitality (P = .031); and CRQ mastery (P = .007). There was a dose-dependent improvement in CRQ dyspnea scores (P < .05) with significant improvements only in the DM-training and DM-exposure groups. CONCLUSION: Exercise training substantially improved the impact of a dyspnea self-management program with a home walking prescription (DM). This impact tended to be dependent on the “dose” of exercise.

The genesis of dyspnea is complex. It appears to be related to central respiratory drive although prevailing leg fatigue could independently potentiate dyspnea. We hypothesized that experimentally induced leg fatigue generates more intense exertional dyspnea for a given level of ventilatory drive. Following familiarization, 19 healthy subjects (32.2 ± 7.6 yr; 11 men) performed a 5-min treadmill test (speed: ∼4 km/h; grade: ∼25%) on two separate days randomized between control (C) and experimentally induced leg fatigue (E) achieved by repeated knee extension against 40% body weight until task failure. Oxygen uptake (V̇o2, l/min), carbon dioxide output (V̇co2, l/min), ventilation (V̇e, l/min), and respiratory rate (fR) were measured breath by breath. Heart rate (HR) and perceived dyspnea intensity (0–10 numerical scale) were recorded continuously. Data were averaged over 30-s intervals. Exertional dyspnea during E was statistically significantly higher (E vs. C: 4.2 ± 0.2 vs. 3.4 ± 0.2, P < 0.001) and accompanied by a significant increase in V̇e (E vs. C: 61.7 ± 3.7 vs. 55.3 ± 2.8, P = 0.005) and fR (E vs. C: 26.7 ± 1.0 vs. 24.2 ± 1.3, P = 0.036). Dyspnea following E remained significantly higher after allowing for the V̇e confound (ANCOVA, P = 0.003). V̇o2, V̇co2, and HR were not significantly different between two conditions. However, the slopes for dyspnea vs. V̇o2 and dyspnea vs. V̇e were similar between E and C, which suggested that gain in dyspnea per unit change in V̇o2 or V̇e was not altered by leg fatigue. These findings support the hypothesis that the intensity of exertional dyspnea is exacerbated by peripheral afferent information from fatigued leg muscles.

Background This study documents the impact of different exercise modalities on dyspnea and leg fatigue during equivalent cardiopulmonary stress in healthy subjects. Methodology Following a familiarization, 20 subjects (age 21–44 years; 8 males) performed six 5-min exercise tests, randomized among: 2 steep slope treadmill tests (25% grade), 2 lesser slope treadmill tests (12% grade) and 2 bicycle tests on 3 separate days. Subjects reported either dyspnea or leg fatigue during each test. Oxygen consumption ( V ˙ O 2 ) , ventilation ( V ˙ E ) , respiratory rate (fR) and heart rate (HR) were measured during each test. Results V ˙ O 2 , V ˙ E , HR, dyspnea and leg fatigue were not significantly different among the three exercise conditions (p > 0.05). Conclusion These findings indicate that at equivalent levels of cardiopulmonary stress reflected by similar levels of V ˙ O 2 and heart rate, the perceived level of exertional dyspnea is not influenced by different patterns of neuromuscular activity. Similarly, the intensity of leg fatigue primarily reflects whole body work and is independent of different patterns of neuromuscular activity.

1. Positron emission tomography (PET) was used to identify the neuroanatomical correlates underlying 'central command' during imagination of exercise under hypnosis, in order to uncouple central command from peripheral feedback. 2. Three cognitive conditions were used: condition I, imagination of freewheeling downhill on a bicycle (no change in heart rate, HR, or ventilation, V(I)): condition II, imagination of exercise, cycling uphill (increased HR by 12 % and V(I) by 30 % of the actual exercise response): condition III, volitionally driven hyperventilation to match that achieved in condition II (no change in HR). 3. Subtraction methodology created contrast A (II minus I) highlighting cerebral areas involved in the imagination of exercise and contrast B (III minus I) highlighting areas activated in the direct volitional control of breathing (n = 4 for both; 8 scans per subject). End-tidal P(CO(2)) (P(ET,CO(2))) was held constant throughout PET scanning. 4. In contrast A, significant activations were seen in the right dorso-lateral prefrontal cortex, supplementary motor areas (SMA), the right premotor area (PMA), superolateral sensorimotor areas, thalamus, and bilaterally in the cerebellum. In contrast B, significant activations were present in the SMA and in lateral sensorimotor cortical areas. The SMA/PMA, dorso-lateral prefrontal cortex and the cerebellum are concerned with volitional/motor control, including that of the respiratory muscles. 5. The neuroanatomical areas activated suggest that a significant component of the respiratory response to 'exercise', in the absence of both movement feedback and an increase in CO(2) production, can be generated by what appears to be a behavioural response.

Breathing sensations of AIR HUNGER, WORK and EFFORT may depend on projections of central motor discharge (corollary discharge) to the forebrain. Source of motor drive (brainstem or cortex) may determine what is perceived. To test the effect of changing motor discharge at constant ventilation, we induced partial neuromuscular blockade during hypercapnic hyperpnea (31 + or - 9 L min(-1); PET(CO(2))=49 + or - 2 Torr) and during matched volitional hyperpnea (34 + or - 5 L min(-1); PET(CO(2))=41 + or - 1 Torr). Decline of vital capacity was similar between conditions (39%). Ventilation was unchanged with paralysis, indicating increased respiratory motor drive to maintain hyperpnea. Sensations were rated on a seven point ordinal scale. Median EFFORT and WORK increased 3-3.5 points with paralysis during both forms of hyperpnea (P0.02, Wilcoxon signed rank). Median AIR HUNGER increased 2.5 points with paralysis during hypercapnic (P0.02) but not during volitional hyperpnea. Data suggests that EFFORT and WORK arise from motor cortex activity (subjects reported engaging volitional control when paralyzed even during hypercapnia) and suggests that AIR HUNGER arises from medullary motor activity.

We have determined whether changes in [Formula: see text]above and below eucapnia modulate the precision of the voluntary control of breathing. Twelve trained subjects performed a compensatory tracking task in which they had to maintain the position of a cursor (perturbed by a variable triangular forcing function) on a fixed target by breathing in and out of a spirometer (ventilatory tracking; at 10 l/min). Before each task, subjects hyperventilated for 5 min, and the end-tidal [Formula: see text]([Formula: see text]) was controlled; tracking was then performed separately at hypocapnia, eucapnia, and hypercapnia ([Formula: see text] ∼25, 37, and 43 Torr, respectively). Ventilatory tracking error was unchanged during hypocapnia ( P > 0.05) but was significantly worse during hypercapnia ( P < 0.003), compared with eucapnia; arm tracking error, performed as a control, was not significantly affected by[Formula: see text]( P > 0.05). In conclusion, ventilatory tracking performance is unaffected by the eucapnic[Formula: see text]. From this, we suggest that resting breathing in awake humans may be independent of chemical drives and of the prevailing [Formula: see text].

Human cerebral activity with increasing inspiratory force: a study using positron emission tomography. J. Appl. Physiol. 81(3): 1295-1305, 1996.--The major aim of this study was to use positron emission tomography (PET) to assess dose-dependent effects of inspiratory loads on relative regional cerebral blood flow as an indication of neuronal activation and recruitment. Six normal men underwent H2 15O-PET scanning during unloaded breathing and with external inspiratory loads (generating mouth pressures of -5, -10, and -15 cmH2O); positive-pressure ventilation against relaxed respiratory muscles acted as control. During unloaded breathing, the supplementary motor area was significantly activated. With the addition of the smallest load, activations also occurred in the right premotor area and bilaterally in the superolateral motor cortex (MI) in areas previously shown to be activated with deeper breathing. There was little further change in these areas with greater loads. Additional force-related activations occurred in the inferolateral sensorimotor cortex, parietal cortex, and midbrain/hypothalamus. The results suggest that volitionally induced increases in inspiratory muscle force are achieved via a complex integration of neuronal activations in cortical and subcortical regions associated with motor control.

The increase in PCO2 that occurs during sleep may reflect an inadequate ventilatory compensation to an increase in upper airway resistance. To address this question in humans, we examined changes in breathing during wakefulness and non-rapid-eye-movement sleep in eight laryngectomized subjects who breathed through a tracheal stoma. In these subjects, any sleep-related increase in upper airway resistance could not affect ventilation. Healthy subjects breathing via an intact upper airway were studied as controls. The mean increase in end-tidal PCO2 from wakefulness to sleep was 2.7 +/- 2.6 (SD) Torr (P = 0.05) in laryngectomized subjects and 1.6 +/- 1.4 Torr (P = 0.02) in control subjects. During wakefulness, ventilation was lower in laryngectomized subjects compared with control subjects, although this difference was not statistically significant (6.8 +/- 1.9 vs. 7.4 +/- 1.2 l/min; P > 0.05). During sleep, the fall in ventilation was similar in the two groups (1.1 +/- 2.1 vs. 0.8 +/- 2.1 l/min; P > 0.05). Our observations are not consistent with the view that increases in upper airway resistance are obligatory for sleep-related CO2 retention in humans.

1. The role of supra-brainstem structures in the ventilatory response to inhaled CO2 is unknown. The present study uses positron emission tomography (PET), with infusion of H2(15)O, to measure changes in relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during CO2-stimulated breathing (CO2-SB) in awake man. 2. Five male volunteers were scanned during CO2-SB (mean +/- S.E.M.; end-tidal PCO2, 50.3 +/- 1.7 mmHg; respiratory frequency, 16.4 +/- 2.7 min-1; tidal volume, 1.8 +/- 0.2 l). As control, scans were performed during 'passive' isocapnic (elevated fraction of inspired CO2) positive pressure ventilation (end-tidal PCO2, 38.4 +/- 1.0 mmHg; respiratory frequency, 15.5 +/- 2.2 min-1; tidal volume, 1.6 +/- 0.2 l). With CO2-SB, all subjects reported dyspnoea. 3. The anatomical locations of the increases in relative rCBF (CO2-SB versus control) were obtained using magnetic resonance imaging. 4. Group analysis identified neuronal activation within the upper brainstem, midbrain and hypothalamus, thalamus, hippocampus and parahippocampus, fusiform gyrus, cingulate area, insula, frontal cortex, temporo-occipital cortex and parietal cortex. No neuronal activation was seen within the primary motor cortex (at sites previously shown to be associated with volitional breathing). 5. These results suggest neuronal activation within the limbic system; this activation may be important in the sensory and/or motor respiratory responses to hypercapnia in awake man.

1. The cardiorespiratory response to imagination of previously performed treadmill exercise was measured in six competitive sportsmen and six non-athletic males. This was compared with the response to a control task (imaging letters) and a task not involving imagination ('treadmill sound only'). 2. In athletes, imagined exercise produced increases in ventilation which varied within and between subjects. The mean maximal increase (11.71 min-1) was approximately 20% of the ventilatory response to actual exercise. This was primarily due to treadmill speed-related increases in respiratory frequency (mean maximal increase, 14.8 breaths min-1) and resulted in significant reductions in end-tidal PCO2 (mean maximal fall, 7 mmHg). These effects were greater (P < 0.01) than any observed during the control tasks. 3. Changes in heart rate (mean increase, 12 beats min-1) were not significantly different from those observed during the control tasks (P > 0.2). 4. In non-athletes, imagination of exercise produced no changes in cardiorespiratory variables. No significant differences were detected in subjective assessments of movement imagery ability between athletes and non-athletes (P = 0.17). 5. This study demonstrates that ventilatory effects, when observed, are specific to imagination of exercise. The greater likelihood of generating ventilatory responses in highly trained athletes, experienced in 'rhythmic' sports, may be related to awareness of breathing and its role in exercise imagination strategy. A volitional component of the response cannot be discounted.