Breathlessness In Chronic Obstructive Pulmonary Disease Research Articles

Opioids in Treatment of Refractory Dyspnea in Chronic Obstructive Pulmonary Disease: Yes, No or Maybe.

Chronic Obstructive Pulmonary Disease (COPD) is a complex condition with significant impact on prognosis, especially in advanced stages where symptom burden becomes critical. Breathlessness affects patients' quality of life, and despite various therapeutic strategies, the role of opioids in palliative care for COPD remains under investigation. The acceptance of a therapeutic trial of different types of opioids is increasing not only in end-of-life situations but also for stable COPD patients experiencing intolerable refractory breathlessness despite optimal conventional therapy. Recent clinical trials have raised questions about the overall clinical benefit of opioids in addressing breathlessness in COPD, prompting the need to clarify inconsistencies and identify specific subgroups that may benefit from opioid therapy. In the clinical setting, it is crucial to understand the attributes of patients who exhibit positive responses to opioids and what type of opioids could have a positive impact. This research paper aims to offer an update of the most recent evidence of opioid treatment in managing breathlessness among individuals with COPD with a head-to-head evaluation of the supporting and opposing proof in the medical literature.

Low-Dose Morphine Does Not Cause Sleepiness in COPD: A Secondary Analysis of a Randomized Trial.

Regular, low-dose, sustained-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, effects on daytime sleepiness, perceived sleep quality and daytime function have not been rigorously investigated. Determine the effects of regular, low-dose, sustained-release morphine on sleep parameters in COPD. Pre-specified secondary analyses of validated sleep questionnaire data from a randomized trial of daily, low-dose, sustained -release morphine versus placebo over four weeks commencing at 8mg or 16mg/day with blinded up-titration over two weeks to a maximum of 32mg/day. Primary outcomes for these analyses were week-1 Epworth Sleepiness Scale (ESS) and Karolinska Sleepiness Scale (KSS) responses on morphine versus placebo. Secondary outcomes included Leeds Sleep Evaluation Questionnaire (LSEQ) scores (end of weeks 1 and 4), KSS and ESS beyond week-1 and associations between breathlessness, morphine, and questionnaire scores. 156 people were randomized. Week-1 sleepiness scores were not different on morphine versus placebo (∆ESS [95%CI] versus placebo: 8mg group: -0.59 [-1.99, 0.81], p=0.41; 16mg group: -0.72 [-2.33, 0.9], p=0.38; ∆KSS versus placebo: 8mg group: 0.11 [-0.7, 0.9], p=0.78; 16mg group: -0.41 [-1.31, 0.49], p=0.37). This neutral effect persisted at later timepoints. In addition, participants who reported reduced breathlessness with morphine at 4 weeks also had improvement in LSEQ domain scores including perceived sleep quality and daytime function. Regular, low-dose morphine does not worsen sleepiness when used for breathlessness in COPD. Individual improvements in breathlessness with morphine may be related to improvements in sleep.

Anxiety and Depression in Chronic Obstructive Pulmonary Disease: Perspectives on the Use of Hypnosis.

Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent and debilitating respiratory condition, characterized by chronic airflow limitation, breathlessness, and other persistent respiratory symptoms. Critically, patients suffering from COPD often find themselves trapped in a vicious comorbidity cycle: while breathlessness and increased respiratory rate are known inducers of anxiety, the latter have been shown in turn to exacerbate breathlessness and chest discomfort. Hypnosis holds great potential for the simultaneous complementary management of anxiety and breathlessness in COPD. It is an inexpensive psychological intervention tailored to the patient’s own experience, convenient in terms of logistics and implementation. In this short qualitative review, we present hypnosis’ structural, cognitive, and neural fundamentals, and assess existing instances of hypnosis use in the treatment of anxiety, depression, and respiratory disease. We then discuss its potential as a tool for improving health-related quality of life and the self-management of COPD within (and beyond) pulmonary rehabilitation.

Breathlessness in COPD: linking symptom clusters with brain activity.

BackgroundCurrent models of breathlessness often fail to explain disparities between patients' experiences of breathlessness and objective measures of lung function. While a mechanistic understanding of this discordance has thus far remained elusive, factors such as mood, attention and expectation have all been implicated as important modulators of breathlessness. Therefore, we have developed a model to better understand the relationships between these factors using unsupervised machine learning techniques. Subsequently we examined how expectation-related brain activity differed between these symptom-defined clusters of participants.MethodsA cohort of 91 participants with mild-to-moderate chronic obstructive pulmonary disease (COPD) underwent functional brain imaging, self-report questionnaires and clinical measures of respiratory function. Unsupervised machine learning techniques of exploratory factor analysis and hierarchical cluster modelling were used to model brain–behaviour–breathlessness links.ResultsWe successfully stratified participants across four key factors corresponding to mood, symptom burden and two capability measures. Two key groups resulted from this stratification, corresponding to high and low symptom burden. Compared with the high symptom burden group, the low symptom burden group demonstrated significantly greater brain activity within the anterior insula, a key region thought to be involved in monitoring internal bodily sensations (interoception).ConclusionsThis is the largest functional neuroimaging study of COPD to date, and is the first to provide a clear model linking brain, behaviour and breathlessness expectation. Furthermore, it was possible to stratify participants into groups, which then revealed differences in brain activity patterns. Together, these findings highlight the value of multimodal models of breathlessness in identifying behavioural phenotypes and for advancing understanding of differences in breathlessness burden.

Cost-effectiveness of sustained-release morphine for refractory breathlessness in COPD: A randomized clinical trial.

Chronic breathlessness is a frequent symptom in advanced Chronic Obstructive Pulmonary Disease (COPD) and has major impact on quality of life, daily activities and healthcare utilization. Morphine is used as palliative treatment of chronic breathlessness. The aim is to analyze cost-effectiveness of regular, low-dose morphine in patients with advanced COPD from a healthcare and societal perspective. In a randomized controlled trial, participants with advanced COPD were assigned to 10mg regular, oral sustained-release morphine or placebo twice daily for four weeks. Quality of life (COPD Assessment Test; CAT), quality-adjusted life years (QALY's; EQ-5D-5L), healthcare costs, productivity, and patient and family costs were collected. Incremental cost-effectivity ratio's (ICERs) using healthcare costs and CAT scores, and incremental cost-utility ratio's (ICURs) using societal costs and QALY's were calculated. Data of 106 of 124 participants were analyzed, of which 50 were in the morphine group (mean [SD] age 65.4 [8.0] years; 58 [55%] male). Both ICER and ICUR indicated dominance for morphine treatment. Sensitivity analyses substantiated these results. From a healthcare perspective, the probability that morphine is cost-effective at a willingness to pay €8000 for an minimal clinically important difference of 2 points increase in CAT score is 63%. From a societal perspective, the probability that morphine is cost-effective at a willingness to pay €20,000 per QALY is 78%. Morphine for four weeks is cost-effective regarding the healthcare and the societal perspective. To estimate the long-term costs and effects of morphine treatment, a study of longer follow-up should be performed. ClinicalTrials.gov (NCT02429050).

Breathlessness and opioid prescribing in COPD in general practice: a cross-sectional, observational study.

Chronic breathlessness is a disabling syndrome, prevalent in people with advanced chronic obstructive pulmonary disease (COPD). Regular, low-dose, oral sustained-release morphine is approved in Australia to reduce symptomatic chronic breathlessness. We aimed to determine the current prescribing patterns of opioids for chronic breathlessness in COPD in Australian general practice and to define any associated patient and practitioner characteristics.Five years (2011 to 2016) of the Bettering the Evaluation and Care of Health database, an Australian national, continual, cross-sectional study of clinical care in general practice were used. The database included 100 consecutive clinical encounters from almost 1000 general practitioners annually (n=488 100 encounters). Descriptive analyses with subsequent regression models were generated.Breathlessness as a patient-defined reason for encounter was identified in 621 of 4522 encounters where COPD was managed. Opioids were prescribed in 309 of 4522 encounters where COPD was managed (6.8%; (95% CI) 6.1–7.6), of which only 17 were prescribed for breathlessness, and the rest for other conditions almost entirely related to pain. Patient age (45–64 years versus age 80+ years, OR 1.68; 1.19–2.36), Commonwealth Concession Card holders (OR 1.70; 1.23–2.34) and socioeconomic disadvantage (OR 1.30; 1.01–1.68) were associated with increased likelihood of opioid prescription at COPD encounters. The rate of opioid prescriptions rose over the 5 years of study.In primary care encounters for COPD, opioids were prescribed in 6.8% of cases, but almost never for breathlessness. These data create a baseline against which to compare changes in prescribing as the treatment of chronic breathlessness evolves.

Prevalence and management of chronic breathlessness in COPD in a tertiary care center

BackgroundBreathlessness is the prominent symptom of chronic obstructive pulmonary disease (COPD). Despite optimal therapeutic management including pharmacological and non-pharmacological interventions, many COPD patients exhibit significant breathlessness. Chronic breathlessness is defined as breathlessness that persists despite optimal treatment of the underlying disease. Because of the major disability related to chronic breathlessness, symptomatic treatments including opioids have been recommended by several authors. The prevalence of chronic breathlessness in COPD and its management in routine clinical practice have been poorly investigated. Our aim was to examine prevalence, associated characteristics and management of chronic breathlessness in patients with COPD recruited in a real-life tertiary hospital-based cohort.MethodsA prospective study was conducted among 120 consecutive COPD patients recruited, in stable condition, at Nancy University Hospital, France. In parallel, 88 pulmonologists of the same geographical region were asked to respond to an on-line questionnaire on breathlessness management.ResultsSixty four (53%) patients had severe breathlessness (modified Medical Research Council scale≥3), despite optimal inhaled medications for 94% of them; 40% had undergone pulmonary rehabilitation within the past 2 years. The severity of breathlessness increased with increasing airflow limitation. Breathlessness was associated with increased symptoms of anxiety, depression and with osteoporosis. No relation was found with other symptoms, exacerbation rate, or cardiovascular comorbidities. Among the patients with chronic breathlessness and Hospitalized Anxiety and/or Depression score > 10, only 25% were treated with antidepressant or anxiolytic. Among the pulmonologists 46 (52%) answered to the questionnaire and expressed a high willingness to prescribe opioids forchronic breathlessness, which contrasted with the finding that none of these patients received such treatments against breathlessness.ConclusionTreatment approaches to breathlessness and associated psychological distress are insufficient in COPD. This study highlights underuse of pulmonary rehabilitation and symptomatic treatment for breathlessness.

Pathophysiological mechanisms of exertional breathlessness in chronic obstructive pulmonary disease and interstitial lung disease.

Breathlessness is a common and distressing symptom in patients with chronic obstructive pulmonary disease (COPD) and fibrotic interstitial lung disease (ILD), particularly during exercise. Effective medical management of exertional breathlessness in people living with COPD and fibrotic ILD is challenging for healthcare providers and requires an understanding of its mechanisms. Thus, in this brief review we summarize recent advances in our understanding of the pathophysiological mechanisms of exertional breathlessness in COPD and fibrotic ILD. The collective results of recent physiological and clinical trials suggest that higher intensity ratings of exertional breathlessness in both COPD and fibrotic ILD compared to healthy control individuals is mechanistically linked to the awareness of greater neural respiratory drive (quantified using inspiratory muscle electromyography) needed to compensate for pathophysiological abnormalities in respiratory mechanics and pulmonary gas exchange efficiency. Any therapeutic intervention capable of decreasing intrinsic mechanical loading of the respiratory system and/or increasing pulmonary gas exchange efficiency has the potential to decrease the prevalence and severity of activity-related breathlessness and improve related clinical and patient-reported outcomes (e.g., exercise tolerance and health-related quality of life) by decreasing neural respiratory drive in people with COPD and fibrotic ILD.

Dysfunctional breathing is more frequent in chronic obstructive pulmonary disease than in asthma and in health

Involuntary adaptations of breathing patterns to counter breathlessness may lead to dysfunctional breathing in obstructive lung diseases. However, no studies examining dysfunctional breathing in Chronic Obstructive Pulmonary Disease (COPD) have been reported.Patients with verified COPD (n=34), asthma (n=37) and a healthy control group (n=41) were recruited. All participants completed the Nijmegen questionnaire for dysfunctional breathing as well as measures of disease activity. Comparisons between groups employed analysis of variance with post-hoc Bonferroni analyses and Pearson correlation for associations.Patients with COPD had significantly higher Nijmegen questionnaire scores than asthmatics (COPD: 23.4±10.6 versus 17.3±10.6, p=0.016) and healthy individuals (14.3±9.6, p=0.002). Significantly more patients with COPD had severe dysfunctional breathing with Nijmegen scores >23 (47%; 16/34) compared to asthma (27%; 10/37) and healthy controls (17%; 7/41) respectively (p=0.019).Dysfunctional breathing was detected in ∼50% of patients with COPD, more so than in asthma or health. Strategies to reduce abnormal breathing behaviours may have important benefits for treatment of breathlessness in COPD.

Junior doctors' attitudes to opioids for refractory breathlessness in patients with advanced chronic obstructive pulmonary disease.

Refractory breathlessness is a common, distressing symptom in patients with advanced chronic obstructive pulmonary disease (COPD). The judicious, off-licence prescription of opioids, together with other management strategies, can improve breathlessness, however, internationally there is profound reluctance to prescribe opioids for breathlessness in COPD. To understand Australian junior doctors' knowledge and attitudes regarding the management of refractory breathlessness and the role of opioids in COPD. All junior doctors undertaking basic training in internal medicine in Victoria were invited to complete an online survey. Knowledge, willingness, and experience prescribing opioids to COPD patients with refractory breathlessness, were examined. Of the 243 responses received, most trainees (193, 86.5%) believed opioids have a role in treating refractory breathlessness in stable COPD outpatients, with 143 (64.1%) recommending morphine as first-line treatment for refractory breathlessness. One quarter (55, 24.7%) reported having themselves initiated an opioid and 102 (45.7%) had prescribed an opioid under senior supervision for management of breathlessness in COPD. Concern regarding adverse opioid effects was low, with 58 (26.0%) having no concerns prescribing an opioid to COPD patients. This is the first study of doctors to demonstrate high awareness, confidence, willingness and experience in prescribing opioids for the off-licence indication of refractory breathlessness in COPD. These findings differ significantly from attitudes reported overseas and are unexpected given the doctors surveyed were recently qualified. The low awareness of possible adverse events and limited insight regarding knowledge gaps is concerning and highlights the significant need for greater education in palliative care.

Short burst oxygen therapy in COPD: A practice nurse's guide

Short burst oxygen therapy (SBOT) is often incorrectly used as a treatment for breathlessness in COPD. Michael Scott provides the evidence around SBOT, so that practice nurses can advise their patients appropriately Chronic obstructive pulmonary disease (COPD) often makes up a large part of a practice nurse's duty. A main part of their responsibility for COPD includes completing annual reviews, which aim to review disease progression and symptom management. Breathlessness is the primary symptom for suffers of COPD, yet the hardest to manage. Short burst oxygen therapy (SBOT) is often incorrectly used as a treatment. Various studies have shown that SBOT does not offer any benefit in the management of breathlessness. Practice nurses should be aware of this evidence so that they can counsel patients effectively.

Comparison of respiratory health-related quality of life in patients with intractable breathlessness due to advanced cancer or advanced COPD

ObjectivesBreathlessness is common in patients with advanced cancer and almost universal in advanced chronic obstructive pulmonary disease (COPD), but studies suggest their experiences of breathlessness vary. This report builds on...

Effect of increasing respiratory rate on airway resistance and reactance in COPD patients.

Airway resistance and reactance measured by forced oscillometry have been used to measure the severity of airway obstruction in chronic obstructive pulmonary disease (COPD) patients. The aims of this study were to assess the effects of tachypnoea on airway resistance and reactance and to correlate these with the severity of dyspnoea. We also evaluated the effects of short-acting β2-agonist (SABA) on these measurements. Airway resistance and reactance were measured with an impulse oscillation system (IOS) in 20 COPD and 10 control participants during resting respiration and metronome-paced breathing at 20, 30 and 40 tidal breaths/min. The same measurements were made for COPD patients after SABA inhalation. Dyspnoea was evaluated using the modified Medical Research Council (MRC) scale. In patients with COPD, higher respiratory rates increased expiratory and inspiratory resistance at 5 Hz (R5), the difference in respiratory resistance at 5 Hz and 20 Hz (R5-R20), resonant frequency and decreased expiratory reactance. The decreases in expiratory reactance from 20 to 40 tidal breaths/min were significantly correlated with MRC scores. SABA inhalation significantly reduced the effect of increased respiratory rate on the reactance measurements. Characteristic changes in IOS measurements, particularly expiratory reactance, induced by increased respiratory rates, were correlated with severity of dyspnoea in COPD patients during their daily lives. IOS and paced breathing may be useful for assessing breathlessness in COPD.

Neural respiratory drive and breathlessness during incremental cycle and treadmill exercise in chronic obstructive pulmonary disease

BackgroundBreathlessness is an important cause of exercise limitation and reduced quality of life for patients with chronic obstructive pulmonary disease (COPD). One of the challenges of breathlessness management in COPD is the lack of physiological markers that reliably correlate with patients' symptoms. The aim of this study was to test the hypothesis that neural respiratory drive (NRD), measured with diaphragm electromyogram (EMGdi) activity, is closely related to breathlessness in COPD. We also investigated whether neuroventilatory uncoupling, which is the dissociation of ventilation from NRD as a consequence of abnormal pulmonary mechanics, contributes to breathlessness intensity over an awareness of levels of NRD alone. MethodsEMGdi and ventilation were measured continuously during exhaustive incremental cycle and treadmill exercise in 12 patients with COPD (mean FEV1 38·7% predicted [SD 14·5]). EMGdi was expressed as a percentage of maximum (EMGdi%max), and relative to tidal volume expressed as a percentage of predicted vital capacity (EMGdi%max/VT%VCpred) to measure neuroventilatory uncoupling. Breathlessness (modified Borg scale) was recorded at baseline, at the end of each minute of exercise, and at completion of exercise. Linear regression analysis was used to determine the associations between breathlessness, EMGdi%max, neuroventilatory uncoupling, and ventilation. FindingsEMGdi%max was closely related to breathlessness in both cycle (r=0·98, p=0·0001) and treadmill exercise (r=0·94, p=0·005), this association being at least as strong as that between neuroventilatory uncoupling and breathlessness (cycle r=0·94, p=0·005; treadmill r=0·91, p=0·01). The association between breathlessness and ventilation was poor when expansion of tidal volume became restricted, whereas the association between EMGdi%max and breathlessness remained close. InterpretationEMGdi%max is closely related to the intensity of exertional breathlessness in COPD. These data suggest that breathlessness in COPD can be largely explained by an awareness of levels of NRD, rather than the association between NRD and achieved ventilation. EMGdi%max could provide a useful physiological biomarker for breathlessness, with advantages over mechanical and ventilatory indices in COPD and the many other diseases in which neuroventilatory uncoupling occurs. FundingUK Medical Research Council, British Council.

The Experience of Breathlessness: The Social Course of Chronic Obstructive Pulmonary Disease

There is a trend toward extending palliative care to nonmalignant diseases. There is no evidence that chronic obstructive pulmonary disease (COPD) requires its own model. The aim of this study was to investigate how the experience of breathlessness in COPD influences patients' attitudes toward the end of life and their quality of life. Eighteen patients were purposively sampled. Data were collected through in-depth interviews and participant observation during outpatient consultations. Narrative methods were used to analyze the data. Treatment-seeking in COPD deviated from prototypical trajectories. Contact with health care was postponed to crisis point. Treatment did not follow diagnosis because of how the diagnosis was given. Help was sought when the symptom had acquired meaning in a person's life. The future did not feature in the interviews. Good communication practices are fundamental in the care for COPD patients. Particularly, diagnosis and prognosis need to be rethought in a model to suit the condition of COPD.

Review: walking aids, chest-wall vibration, and neuroelectrical muscle stimulation relieve breathlessness in COPD

C Bausewein Dr C Bausewein, King’s College London, London, UK; claudia.bausewein@kcl.ac.uk In advanced disease, do non-pharmacological and non-invasive interventions relieve breathlessness? Studies selected evaluated non-pharmacological or non-invasive interventions for breathlessness...

Progressive breathlessness in COPD — The role of hyperinflation and its pharmacological management

Breathlessness, along with the associated inability to engage in normal activity, is one of the most distressing symptoms for patients with chronic obstructive pulmonary disease (COPD). If treatment for breathlessness is started early in the disease, physical activity could, in theory, be improved or maintained; this may slow the progression of symptoms towards disability and improve quality of life. A significant cause of breathlessness in COPD is hyperinflation of the lungs due to air trapping, which occurs largely as a result of airflow limitation. Regular exercise reduces the respiratory demand of muscles and, by inference, the impact of air trapping during less intensive activities. Moreover, although airflow limitation in COPD is poorly responsive to anti-inflammatory drugs and less responsive to bronchodilators than in asthma, bronchodilators are clinically proven to bring perceivable symptom improvements in COPD. These improvements correlate with improvements in air trapping indices, which can be significant even in the absence of significant change in forced expiratory volume in 1 second (FEV(1)). The rationale for treatment in COPD, therefore, differs to that for asthma. Understanding of the pathophysiology of COPD improves our chances of achieving an effective intervention with the hope of a better quality of life for patients.

Alternative methods for assessing bronchodilator reversibility in chronic obstructive pulmonary disease

BACKGROUNDBronchodilator reversibility testing is recommended in all patients with chronic obstructive pulmonary disease (COPD) but does not predict improvements in breathlessness or exercise performance. Two alternative ways of assessing lung...

Alternative methods for assessing bronchodilator reversibility in chronic obstructive pulmonary disease

BACKGROUNDBronchodilator reversibility testing is recommended in all patients with chronic obstructive pulmonary disease (COPD) but does not predict improvements in breathlessness or exercise performance. Two alternative ways of assessing lung mechanics—measurement of end expiratory lung volume (EELV) using the inspiratory capacity manoeuvre and application of negative expiratory pressure (NEP) during tidal breathing to detect tidal airflow limitation—do relate to the degree of breathlessness in COPD. Their usefulness as end points in bronchodilator reversibility testing has not been examined.METHODSWe studied 20 patients with clinically stable COPD (mean age 69.9 (1.5) years, 15 men, forced expiratory volume in one second (FEV1) 29.5 (1.6)% predicted) with tidal flow limitation as assessed by their maximum flow-volume loop. Spirometric parameters, slow vital capacity (SVC), inspiratory capacity (IC), and NEP were measured seated, before and after nebulised saline, and at intervals after 5 mg nebulised salbutamol and 500 μg nebulised ipratropium bromide. The patients attended twice and the treatment order was randomised.RESULTSMean FEV1, FVC, SVC, and IC were unchanged after saline but the degree of tidal flow limitation varied. FEV1improved significantly after salbutamol and ipratropium (0.11 (0.02) l and 0.09 (0.02) l, respectively) as did the other lung volumes with further significant increases after the combination. Tidal volume and mean expiratory flow increased significantly after all bronchodilators but breathlessness fell significantly only after the combination treatment. The initial NEP score was unrelated to subsequent changes in lung volume.CONCLUSIONSNEP is not an appropriate measurement of acute bronchodilator responsiveness. Changes in IC were significantly larger than those in FEV1and may be more easily detected. However, our data showed no evidence for separation of “reversible” and “irreversible” groups whatever outcome measure was adopted.

Chronic exertional dyspnea and respiratory muscle function in patients with chronic obstructive pulmonary disease.

The symptom of breathlessness is an important outcome measure in the management of patients with chronic obstructive pulmonary disease (COPD). Clinical ratings of dyspnea and routine lung function are weakly related to each other. However, in the clinical setting breathlessness in COPD is encountered under conditions of increased respiratory effort, impeded respiratory muscle action, or functional weakness. Thus, the present study was carried out to determine whether and to what extent clinical ratings of dyspnea and respiratory muscle dysfunction relate to each other. In 21 patients with COPD two methods were used to rate dyspnea: a modified Medical Research Council Scale (MRC) and the Baseline Dyspnea Index (BDI), which is a multidimensional instrument for measuring dyspnea based on three components: magnitude of task, magnitude of effort, and functional impairment. A baseline focal score was obtained as the sum of the three components. Measures were: pulmonary volumes; arterial blood gases; maximal voluntary ventilation (MVV); maximal inspiratory and expiratory pressures (MIP and MEP, respectively); and breathing patterns ventilation (VE), tidal volume (VT), and respiratory frequency (Rf). In 15 patients pleural pressure was also measured during both quiet breathing (Pplsw) and maximal inspiratory sniff maneuver at FRC (Pplsn). BDI and MRC ratings related to each other and showed comparable weak associations with standard parameters (FEV1, PaCO2, VT), MIP, and MEP. In contrast, MVV closely and similarly related to both ratings. Pplsw (%Pplsn), a measure of respiratory effort, and Pplsw (%Pplsn)/VT(%VC), an index of neuroventilatory dissociation, related significantly to both the BDI (r2 = -0.77 and r2 = -0.75, respectively) and the MRC (r2 = 0.81 and r2 = 0.74, respectively). Using MVV, Pplsw (%Pplsn), and Pplsw (%Pplsn)/VT(%VC) in a stepwise multiple regression as independent variables with BDI rating as dependent variable, MVV explained an additional 14.5% of the variance of the BDI over the 67.8% predicted by Pplsw (%Pplsn). Our results demonstrate that the level of chronic exertional dyspnea in COPD increases as the ventilatory muscle derangement increases. The level of the relationships among dyspnea ratings and MVV and respiratory effort helps to explain some of the mechanisms of chronic dyspnea of COPD. These measures should be considered for therapeutic intervention to reduce dyspnea.