Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD.

Exogenous opioid drugs, such as morphine, relieve breathlessness. The present study hypothesis was that endogenous opioids, released during the stress of exercise, modify dyspnoea in patients with chronic obstructive pulmonary disease. After familiarisation, patients performed an incremental treadmill exercise test followed by constant work on the treadmill for 10 min. At subsequent visits (2 to 3 days apart), patients received two puffs of albuterol, had a catheter placed in an arm vein for removal of blood to measure beta-endorphin immunoreactivity, received normal saline or 10 mg of naloxone intravenously in randomised order, and then performed high-intensity constant work rate exercise on the treadmill. The mean+/-sd age of the 17 patients (eight females and nine males) was 63+/-7 yrs, and post-bronchodilator forced expiratory volume in one second was 50+/-17% predicted. In both conditions, beta-endorphin levels increased three-fold from rest to end-exercise. The regression slope of breathlessness as a function of oxygen consumption (primary outcome), mean ratings of breathlessness throughout exercise and peak ratings of breathlessness were significantly higher with naloxone than normal saline. There were no differences in physiological responses throughout exercise between conditions. In conclusion, endogenous opioids modify dyspnoea during treadmill exercise in patients with chronic obstructive pulmonary disease by apparent alteration of central perception.

Outcomes for COPD pharmacological trials: from lung function to biomarkers.

The American Thoracic Society/European Respiratory Society jointly created a Task Force on "Outcomes for COPD pharmacological trials: from lung function to biomarkers" to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

Intratumoral Bacillus Calmette-Guérin immunotherapy prior to surgery for carcinoma of the lung: results of a prospective randomized trial.

A prospective randomized trial of preoperative intratumoral therapy with Bacillus Calmette-Guérin (BCG) was conducted in non-small cell lung cancer patients. Eighty-eight patients (48 BCG-treated and 40 control subjects) were entered into the study; three control subjects were removed from data analysis because histology revealed pathology other than non-small cell lung cancer. There were no differences between BCG-treated and control patients in sex, age, cigarettes smoked per day, pack-years of cigarette smoking, white blood cell count, or number of peripheral blood lymphocytes. Toxicity of BCG was limited to transient malaise and fever (average peak temperature, 38.7 degrees C). There was no significant difference in outcome (recurrence or survival) between BCG-treated and control groups with Stage I or Stage III tumors; there were too few Stage II tumors for separate statistical analysis. Outcome was not affected within or between the two treatment groups by tuberculin skin test status. Combining both treatment groups, Stage III patients had a worse outcome than did Stage I-II patients, non-squamous cell tumor patients (large cell and adenocarcinoma) had worse outcomes than did squamous cell tumor patients, and men had a worse outcome than women. We conclude that, although preoperative intratumoral BCG therapy is safe, it does not lengthen disease-free interval or prolong survival in patients with non-small cell lung cancer.

The measurement of dyspnea during exercise in patients with lung disease.

The measurement of dyspnea during an exercise task provides an opportunity to simulate daily physical activities that lead to breathing difficulty in patients with lung disease. Although the exact stimulus for the sensation of breathlessness is unknown, it is possible to measure dyspnea during exercise by applying the principles of psychophysics to the analysis of various stimulus-response relationships. It is logical to consider that the exercise task, ie, work or power production, causes both physiologic and perceptual responses. A 0 to 10 category scale with ratio properties developed by Borg and a visual analogue scale are the most commonly used instruments for rating the severity of dyspnea during exercise. The ratings of breathlessness are generally reliable over time and are sensitive to evaluate an acute intervention in patients with stable respiratory disease. The exercise intensity-dyspnea relationship appears to be the most appropriate stimulus-response relationship for quantifying dyspnea during exercise.

The role of theophylline in the treatment of dyspnea in COPD.

Dyspnea is influenced by both physiologic and psychologic factors. Breathlessness is common in patients with chronic obstructive pulmonary disease (COPD) and often is the reason that the individual patient seeks medical attention. In order to evaluate the different clinical studies involving the use of theophylline in COPD patients, it is important to consider the three distinct approaches for measuring dyspnea--psychophysical testing, clinical methods, and ratings during exercise. Four randomized, double-blind, placebo-theophylline trials from one to four weeks in duration have evaluated the impact of theophylline on lung function and breathlessness. In these studies, the overall improvement in forced expiratory volume in one second was quite consistent for theophylline compared with placebo therapy. When appropriate clinical methods for measuring dyspnea were used, theophylline showed a positive reduction in breathlessness. These reports suggest that theophylline provides modest objective and subjective improvement in patients with symptomatic chronic air flow obstruction.

How should health-related quality of life be assessed in patients with COPD?

The traditional approach of caring for patients with chronic respiratory disease has been to rely on pulmonary function tests to quantify the severity and to assess response to therapy. However, patients with respiratory conditions seek medical attention because of symptoms, particularly dyspnea, and impaired ability to function, which clearly impact on an individual's health-related quality of life (HRQOL). Accordingly, instruments have been developed to provide a standardized method to measure health status and levels of impairment. One of the major reasons for measuring HRQOL is to detect how much HRQOL has changed in response to therapy (an evaluative instrument). A minimum clinically significant change has been established for some HRQOL instruments in order to indicate the relative value of any measured change and to guide the interpretation as to whether the change is "clinically meaningful." Selected studies using disease-specific instruments have demonstrated that beta(2)-agonist, anticholinergic, and theophylline medications can improve HRQOL, as compared with placebo therapy.

Pulmonary rehabilitation.

There has been a resurgence of interest in pulmonary rehabilitation mainly because the prevalence of COPD has increased, scientific studies document consistent benefits (increased exercise endurance and reduced dyspnea), and thoracic surgeons recognize that preoperative and postoperative conditioning enhances the results of lung volume reduction surgery and lung transplantation. Although education and psychosocial/behavioral interventions are important components of a multidimensional program, exercise training of the upper and lower extremities is essential to achieve the described improvements. Current programs vary considerably in the frequency, intensity, and duration of exercise reconditioning. Two "key" questions relating to pulmonary rehabilitation are as follows. What is an appropriate training intensity? How should patients monitor the training intensity? Maintenance exercise programs and the development of home- or community-based programs will be important future developments.

Evaluation of clinical methods for rating dyspnea.

To evaluate available clinical methods (self ratings and questionnaire) for rating dyspnea, we (1) compared scores from the recently developed baseline dyspnea index (BDI) with the Medical Research Council (MRC) scale and the oxygen-cost diagram (OCD) in 153 patients with various respiratory diseases who sought medical care for shortness of breath; and (2) evaluated the relationships between dyspnea scores and standard measures of physiologic lung function in the same patients. The dyspnea scores were all significantly correlated (r = 0.48 to 0.70; p less than 0.001). Agreement between two observers or with repeated use was satisfactory with all three clinical rating methods. The BDI showed the highest correlations with physiologic measurements. Dyspnea scores were most highly related to spirometric values (r = 0.78; p less than 0.001) for patients with asthma, maximal respiratory pressures (r = 0.34 and 0.35; p less than 0.001) for patients with chronic obstructive pulmonary disease, and PImax (r = 0.51; p = 0.01) and FVC (r = 0.44; p = 0.03) for those with interstitial lung disease. These results show that: (1) the BDI, MRC scale, and OCD provide significantly related measures of dyspnea; (2) the clinical ratings of dyspnea correlate significantly with physiologic parameters of lung function; and (3) breathlessness may be related to the pathophysiology of the specific respiratory disease. The clinical rating of dyspnea may provide quantitative information complementary to measurements of lung function.

Evaluation of the short-form 36-item questionnaire to measure health-related quality of life in patients with COPD.

STUDY OBJECTIVE: To evaluate the short-form 36-item questionnaire (SF-36) as an instrument for measuring health-related quality of life (HRQL) in patients with symptomatic COPD. DESIGN: Observational data at a single point in time. SETTING: Outpatient pulmonary clinic. PATIENTS: Fifty male patients with COPD and no significant comorbidity. MEASUREMENTS AND RESULTS: HRQL was assessed with the SF-36, which consists of 36 questions that cover nine health domains. Clinical ratings of dyspnea were measured by the multidimensional baseline dyspnea index (BDI). Pulmonary function tests included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximal inspiratory mouth pressure (PImax). The mean (+/- SD) age of the patients was 72 +/- 8 years. The BDI focal score was 5.6 +/- 2.3, FEV1 was 1.32 +/- 0.60 L (48 +/- 22% pred), and PImax was 62 +/- 23 cm H2O. The BDI focal score was significantly correlated with seven of nine components of the SF-36 (range of r, 0.42 to 0.91; p < 0.05). The FEV1 percent of predicted and PImax were significantly correlated with five of nine health components (range of r, 0.30 to 0.65 and 0.31 to 0.61, respectively). Using linear regression model analysis with the different SF-36 components as the dependent variable and BDI, FVC, FEV1, and PImax as independent variables, the BDI score was the only significant predictor of social and physical functioning, role-physical, vitality, pain, health perceptions, and health transition (p < 0.05). CONCLUSIONS: The SF-36 is a valid instrument to measure HRQL in patients with COPD. The severity of dyspnea but not respiratory function was a significant predictor of various components of HRQL.

Dyspnea ratings for prescription of cross-modal exercise in patients with COPD.

STUDY OBJECTIVE: To investigate the ability of patients with COPD to reproduce an exercise intensity accurately on the treadmill using dyspnea ratings obtained during incremental exercise on the cycle ergometer (cross-modal exercise prescription). DESIGN: Five visits over an 8-week period. PATIENTS: Thirteen symptomatic patients with stable COPD. Age was 67+/-6 years (mean+/-SD). FEV1 was 1.15+/-0.22 L (45+/-7% predicted). INTERVENTIONS: At each visit, patients performed spirometry and exercise. Visit 1 was a practice incremental exercise test on the cycle ergometer. At visit 2 (1 week later), patients estimated the intensity of dyspnea using the 0 to 10 category-ratio scale during an incremental exercise test on the cycle ergometer (cycle estimation trial). Visit 3, 5 weeks later, was a practice session on the treadmill. At visit 4, 1 week later, patients were instructed to produce specific intensities of dyspnea (ie, dyspnea targets) at 50% and at anaerobic threshold (AT) or 80% of peak oxygen consumption (VO2) as calculated from results at visit 2 (treadmill production trial). Visit 5, 1 week later, was the treadmill estimation trial. MEASUREMENTS AND RESULTS: Lung function was stable at all visits. Dyspnea ratings were 1.9+/-0.9 at 50% of VO2 and 5.6+/-1.5 at AT/80% of peak VO2 (17.5+/-3.3 mL/kg/min). The VO2 at the treadmill production trial (761+/-185 mL/min) was significantly higher than at the cycle estimation trial (612+/-159 mL/min) at the low dyspnea target (p < 0.0002; upward bias, 26+/-16%). In contrast, there was no significant difference in VO2 values (929+/-176 mL/min vs 948+/-259 mL/min) at the high dyspnea target (p > 0.5; 0+/-11% bias). CONCLUSIONS: Patients with COPD can use dyspnea ratings from an incremental cycle ergometry test to regulate exercise on the treadmill without systematic bias at an intensity of 80% of peak VO2, but exceed the desired VO2 when using the dyspnea rating at an intensity of 50% of peak VO2.

Dyspnea ratings for prescribing exercise intensity in patients with COPD.

STUDY OBJECTIVE: We tested the hypothesis that patients with COPD can use dyspnea ratings obtained from a prior graded exercise test as a target to reliably produce specific exercise intensities. DESIGN: Four visits over a 7-week period. SETTING: Pulmonary function and cardiorespiratory exercise laboratory at a university hospital. PATIENTS: Fifteen symptomatic patients with stable COPD. Age was 68 +/- 7 (mean +/- SD) years. FEV1 was 1.12 +/- 0.22 L (45 +/- 8% predicted). INTERVENTIONS: At each visit, patients estimated the heaviness of weights to evaluate their magnitude estimation of a nonrespiratory task; after pulmonary function testing was completed, patients were tested on the cycle ergometer. At estimation trial 1 (day 0), patients estimated the intensity of dyspnea using the 0 to 10 category-ratio scale during an incremental exercise test. Estimation trial 2 (day 5 to 7) was the same as the previous trial. At production trials 1 (day 10 to 14) and 2 (day 40 to 44), patients were instructed to produce specific intensities of dyspnea (ie, dyspnea targets) at 50% and at anaerobic threshold (AT) or 80% of peak oxygen consumption (Vo2) as calculated from results at estimation trial 2. MEASUREMENTS AND RESULTS: Lung function was stable at all visits. Dyspnea ratings were 1.8 +/- 0.9 (range, 1 to 3) at 50% of peak Vo2 and 5.5 +/- 1.5 (range, 4 to 8) at AT/80% of peak Vo2 (17.0 +/- 3.4 mL/kg/min) at estimation trial 2. The individual percent changes in Vo2 at the lower dyspnea target were 12 +/- 19% and 11 +/- 19% for production trials 1 and 2, respectively, compared with estimation trial 2. At the higher dyspnea target, the corresponding individual percent changes in Vo2 were -4 +/- 9% and -7 +/- 11%, respectively. For all 15 patients, there were borderline statistical differences for the Vo2 values at the lower (p = 0.04 and p = 0.07) and at the higher (p = 0.04 for each production trial) dyspnea targets for production trials 1 and 2 compared with estimation trial 2. Two patients showed 50% or greater variability in the calculated exponent for magnitude estimation of weights. In a subgroup analysis of the 13 patients with reproducible magnitude estimation of the heaviness of weights, there were no significant differences in Vo2 for the two production trials compared with estimation trial 2 at both exercise intensities. CONCLUSIONS: Dyspnea ratings obtained from an incremental exercise test can be used as a target for patients with COPD to regulate/monitor the intensity of exercise training. The ability of patients with COPD to achieve a desired Vo2 based on an individual dyspnea target was generally more accurate at the higher exercise level (AT/80% of peak Vo2) compared with the lower intensity (50% of peak Vo2). Acceptable accuracy was maintained over a 5-week time period.

Descriptors of breathlessness in healthy individuals: distinct and separable constructs.

STUDY OBJECTIVES: We tested the hypothesis that descriptors of breathlessness represent distinct and separable cognitive constructs, and predicted that the use of descriptors of breathlessness by healthy individuals is the same as their use by patients with cardiopulmonary disease. DESIGN: Cluster analyses obtained in healthy individuals were compared with those obtained previously in patients who complained of breathing discomfort. In addition, we used multidimensional scaling (MDS) techniques to analyze relationships among descriptors in healthy individuals. SETTING: Public university. PARTICIPANTS: The participants were 100 healthy individuals (48 men and 52 women) ranging in age between 18 and 65 years (mean, 27.9+/-11.7 years). MEASUREMENTS AND RESULTS: Participants judged the dissimilarity among pairs of 15 descriptors of breathlessness that were used previously to examine the experience of dyspnea in patients who complained of breathing discomfort. Cluster analysis solutions obtained in the healthy individuals were virtually identical to those obtained previously in patients. Three dimensions (attributes) of breathing discomfort were uncovered with MDS: "Depth and frequency of breathing," "Perceived need, or urge, to breathe," and "Difficulty breathing and phase of respiration." The results did not depend on age, sex, levels of education, or the presence of uncomfortable awareness of breathing with activities. CONCLUSIONS: The relations among descriptors of breathlessness obtained in healthy individuals support the contention that the association of different clusters with different disease states reflects distinct and separable cognitive constructs that are not simply dependent on the presence of an underlying pathophysiology or on a specific disease condition. Our results in healthy individuals also suggest that distinct qualities of breathlessness relate to different physiologic mechanisms underlying respiratory discomfort.

Positional dyspnea and oxygen desaturation related to carcinoma of the lung. Up with the good lung.

Body position can lead to respiratory symptoms and affect gas exchange in disease states. We describe a patient with carcinoma of the left lung in whom dyspnea and oxygen desaturation developed in the right lateral position only. Fiberoptic bronchoscopic study demonstrated a tumor mass protruding into the left main-stem bronchus, which caused further narrowing when the patient turned on his right side.

Salmeterol reduces dyspnea and improves lung function in patients with COPD.

STUDY OBJECTIVE: To investigate the short-term effects of inhaled salmeterol on the perception of dyspnea and lung function in patients with COPD. DESIGN: Double-blind, crossover, randomized trial comparing inhaled salmeterol and inhaled placebo over 4 h. SETTING: Pulmonary function laboratory at university medical center. PATIENTS: Sixteen patients with symptomatic COPD and at least 200-mL increase in FEV1 after inhalation of two puffs (180 microg) of albuterol. INTERVENTIONS: Visit 1 was used for familiarization. At visits 2 and 3 (2 to 3 days apart), patients inhaled either two puffs of salmeterol (42 microg) or placebo. MEASUREMENTS AND RESULTS: Lung function and dyspnea were measured at 0.5, 2, and 4 h after inhalation of the study medication. Dyspnea was measured by the -5 to +5 category scale at rest and by the 0 to 10 category-ratio scale while breathing through inspiratory resistances of 5, 15, and 30 cm H20/L/s. Age was 66+/-8 years (mean+/-SD). FEV1 was 0.97+/-0.331 (51+/-13% predicted). There were significantly higher values for FEV1 and FVC (at all time periods) and lower values for functional residual capacity (at all time periods) and residual volume (at 4 h) with salmeterol than with placebo. There were significantly lower dyspnea ratings on the -5 to +5 category scale (p=0.03 at 2 h and p=0.02 at 4 h) and for the mean dyspnea scores during resistive breathing with salmeterol compared with placebo (p=0.002). CONCLUSIONS: Inhaled salmeterol reduced dyspnea, increased airflow, and reduced hyperinflation over 4 h in patients with symptomatic COPD.

Measurement of respiratory sensation in interstitial lung disease. Evaluation of clinical dyspnea ratings and magnitude scaling.

To evaluate measurements of respiratory sensation in ILD, we compared ratings of breathlessness from three clinical scales with the perceived magnitude of added elastic loads in 20 symptomatic ILD patients. Dyspnea ratings were obtained by two independent observers for each clinical method. Perceived magnitude of four elastic loads was selected from the Borg category scale; these estimates were summarized using the psychophysical power function equation. Ten age-matched healthy subjects also scaled the magnitude of added elastic loads. Dyspnea ratings from the three clinical scales were significantly interrelated. Mean exponents for mouth pressure developed during elastic loading were similar in the patient and control groups. Dyspnea ratings and exponents for elastic loads were not significantly correlated in ILD patients. Of the physiologic parameters examined, Dsb and gas exchange during exercise correlated significantly with clinical dyspnea ratings; none correlated with the exponent for added elastic loads. These data demonstrate that clinical dyspnea ratings provide valid measures of breathlessness in patients with ILD which are independent of the perception of respiratory loads.

Acute effects of passive smoking on lung function and airway reactivity in asthmatic subjects.

We studied the acute effects of one hour of passive cigarette smoking on the lung function and airway reactivity of nine young adult asthmatic volunteers. At the time of this study, the subjects were asymptomatic and had normal or nearly normal lung function. Passive smoking produced no change in expiratory flow rates. However, there was a small decrease in nonspecific bronchial reactivity, as assessed by methacholine inhalation challenge testing (p = 0.022). Pharmacologically active substances present in cigarette smoke, such as nicotine, may explain the observed change in airway reactivity. Although the finding of decreased airway reactivity might suggest that passive smoking produces a "protective" effect on the underlying asthma, the observed change in reactivity was slight and of uncertain clinical significance. We conclude that passive smoking presents no acute respiratory risk to young asymptomatic asthmatic patients.

Right ventricular function at rest and during exercise in chronic obstructive pulmonary disease.

Right ventricular ejection fraction (RVEF), a measure of systolic pump performance of the right ventricle, is frequently depressed at rest or during exercise in patients with chronic obstructive pulmonary disease (COPD). The most common cause of reduced RVEF in COPD is augmentation of right ventricular afterload, namely an increase in pulmonary artery pressure and pulmonary vascular resistance. Therapy with agents that decrease the afterload on the right ventricle have the potential to improve the systolic performance of this chamber. Oxygen, vasodilators such as hydralazine and nifedipine, theophylline, and sympathomimetics all may augment RVEF in part by reducing pulmonary vascular resistance and, in some cases, pulmonary artery pressures in patients with COPD and cor pulmonale. However, only oxygen therapy has been shown to improve survival.

The measurement of dyspnea. Contents, interobserver agreement, and physiologic correlates of two new clinical indexes.

To improve the clinical measurement of dyspnea, we developed a baseline dyspnea index that rated the severity of dyspnea at a single state and a transition dyspnea index that denoted changes from that baseline. The scores in both indexes depend on ratings for three different categories: functional impairment; magnitude of task, and magnitude of effort. At the baseline state, dyspnea was rated in five grades from 0 (severe) to 4 (unimpaired) for each category. The ratings for each of the three categories were added to form a baseline focal score (range, 0 to 12). At the transition period, changes in dyspnea were rated by seven grades, ranging from -3 (major deterioration), to +3 (major improvement). The ratings for each of the three categories were added to form a transition focal score (range, -9 to +9). In 38 patients tested with respiratory disease, interobserver agreement was highly satisfactory for both indexes. The baseline focal score had the highest correlation (r = 0.60; P less than 0.001) with the 12-minute walking distance (12 MW), while significant, but lower, correlations existed for lung function. For the transition focal score, there was a significant correlation only with the 12 MW (r = 0.33; p = 0.04). These results indicate that dyspnea can receive a direct clinical rating that provides important information not disclosed by customary physiologic tests.

Salmeterol plus theophylline combination therapy in the treatment of COPD.

BACKGROUND: Patients with COPD often require multiple therapies to improve lung function and decrease symptoms and exacerbations. Salmeterol and theophylline are indicated for the treatment of COPD, but the use of these agents in combination has not been extensively studied. OBJECTIVES: To compare the efficacy and safety of salmeterol plus theophylline vs either agent alone in COPD. METHODS: Randomized, double-blind, double-dummy, parallel-group trial in 943 patients with COPD. After an open-label theophylline titration period (serum levels, 10 to 20 microg/mL), patients were randomly assigned to receive salmeterol (42 microg bid) plus theophylline, salmeterol (42 microg bid), or theophylline for 12 weeks. Serial pulmonary function tests were completed on day 1 and treatment week 12. Patients kept diary cards and noted their peak flow rates, symptom scores, and albuterol use, and periodically completed quality-of-life and dyspnea questionnaires. RESULTS: All three groups significantly improved compared with baseline. Combination treatment with salmeterol plus theophylline provided significantly (p < or = 0.045) greater improvements in pulmonary function; significantly (p < or = 0.048) greater decreases in symptoms, dyspnea, and albuterol use; and significantly fewer COPD exacerbations (p = 0.023 vs theophylline). In general, treatment with salmeterol provided greater improvement in lung function and satisfaction with treatment compared with theophylline. Salmeterol treatment was also associated with significantly fewer drug-related adverse events (p < or = 0.042) than either treatment that included theophylline. The safety profile (adverse events, vital signs, and ECG findings) of the two treatments that included theophylline were similar. CONCLUSION: Patients with COPD may benefit from combination treatment with salmeterol plus theophylline, without a resulting increase in adverse events or other adverse sequelae.

Impact of dyspnea and physiologic function on general health status in patients with chronic obstructive pulmonary disease.

STUDY OBJECTIVE: To examine the relationship among clinical dyspnea ratings, physiologic pulmonary function, and general health status in symptomatic patients with chronic obstructive pulmonary disease (COPD). DESIGN: Observational data collected at a baseline state. SETTING: Outpatient pulmonary disease clinics at a university hospital and two VA medical centers. PATIENTS: One hundred ten male patients with COPD with no significant comorbidity were recruited. MEASUREMENTS AND RESULTS: Clinical ratings of dyspnea were measured by the multidimensional baseline dyspnea index (BDI). Pulmonary function tests included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximal inspiratory mouth pressure (PImax). General health status was assessed with the Medical Outcomes Study short-form survey, which consists of 20 questions that cover six health components. The mean age of the patients was 67 +/- 8 yr (+/- SD). The mean value for FVC was 2.84 +/- 0.84 L (68 +/- 18 percent of predicted), for FEV1 was 1.28 +/- 0.59 L (44 +/- 17 percent of predicted), and for PImax was 59.0 +/- 25.0 cm H2O. The BDI score and PImax were significantly correlated with five of the six components of general health status. Only three of the six components of general health were significantly correlated with FEV1 as percent predicted (rs value range, 0.30 to 0.44) and with FVC as percent predicted (rs value range, 0.25 to 0.33). Statistical comparisons showed that the BDI score had significantly higher correlations than FVC (percent predicted), FEV1 (percent predicted), and PImax values with physical functioning and role functioning. Multiple linear regression analysis showed that the BDI score was the only statistically significant predictor of role functioning, mental health, and health perceptions for general health status, whereas both the BDI score and FEV1 (percent predicted) were independent predictors of physical functioning and social functioning. CONCLUSION: Dyspnea ratings influence and predict general health status to a greater extent than do physiologic measurements in symptomatic patients with COPD. A shift in focus from the pathophysiology of disease to assessment and relief of symptoms may provide more meaningful benefits for the individual patient in terms of quality of life. This consideration requires that health-care providers use available measuring tools in clinical practice to quantify symptoms, as well as overall health status.