Impact of Chronic Obstructive Pulmonary Disease on Quality of Life: The Role of Dyspnea

The American Journal of Medicine (2006) Vol 119 (10A), S12–S20

Impact of Chronic Obstructive Pulmonary Disease on Quality of Life: The Role of Dyspnea Andrew L. Ries, MD, MPH Department of Medicine and Department of Family and Preventive Medicine, University of California–San Diego, San Diego, California, USA ABSTRACT Dyspnea is a common symptom that accompanies a diagnosis of chronic obstructive pulmonary disease (COPD). Dyspnea often interferes with the patient’s health-related quality of life (HRQOL), yet it is often underreported by the patient and underrecognized by the clinician. Reductions in objective pulmonary function measurements, such as forced expiratory volume in 1 second, are not well correlated with the patient’s perception of symptoms and HRQOL. The patient’s self-reported or subjective assessment is therefore important when evaluating the intensity of dyspnea and its impact on HRQOL. This article describes several well-validated questionnaires and dyspnea assessment scales that can be effective for assessing the intensity and impact that dyspnea may have on patient-perceived HRQOL. In addition, it describes the integration of pulmonary rehabilitation and specific pharmacotherapies as well as how these interventions can positively influence and modify the severity and distress of dyspnea. Effective assessment and therapeutic management of dyspnea for the patient living with COPD are opportunities to improve the patient’s overall HRQOL. © 2006 Elsevier Inc. All rights reserved. KEYWORDS: Chronic obstructive pulmonary disease; Dyspnea; Health-related quality of life; Pharmacologic intervention; Pulmonary rehabilitation; Tiotropium

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Identifying optimal methods for assessing COPD, making an appropriate diagnosis, and evaluating meaningful clinical outcome measurements remain somewhat controversial.1 Objective pulmonary function measurements, such as forced expiratory volume in 1 second (FEV1), provide the clinician with an appropriate means to diagnose, stage severity, and estimate prognosis of COPD. However, reduction in FEV1 is not well correlated with the patient’s perception of symptoms and health-related quality of life (HRQOL).2 In fact, any significant and/or sudden change in the patient’s symptoms may occur against a backdrop of relatively modest changes in pulmonary function. For patients with COPD, dyspnea is associated with a constellation of interrelated Requests for reprints should be addressed to Andrew L. Ries, MD, MPH, University of California, San Diego Medical Center, 200 West Arbor Drive, San Diego, California 92103-8377. E-mail address: [email protected].

0002-9343/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2006.08.003

symptoms that include impaired exercise performance and functional capacity, depression, and anxiety—that together promote disability and interfere with the patient’s HRQOL.3 The pathogenesis of dyspnea (particularly with exertion) is multifactorial and includes several known factors, including dynamic lung hyperinflation; increased ventilatory demand relative to capacity; abnormalities in gas exchange, including hypoxemia and hypercapnia; inspiratory muscle weakness; and cognitive and psychological influences (e.g., fear, anxiety). In patients with COPD, any or all of these factors may play a contributing role.4 Unfortunately, the symptoms of dyspnea are often underreported by the patient and underrecognized by the clinician, especially when COPD is in its early and most treatable stages.1,5 This article reviews the central role of dyspnea as the chief contributor to disability in COPD, it examines the current instruments for assessing dyspnea, and it explores specific interventions that are beneficial in alleviating the symptoms of dyspnea and improving the patient’s HRQOL.

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Table 1 Correlation coefficients between change in breathlessness (Borg scale during exercise) and change in various exercise indices from baseline to highest equivalent work load Change in Borg Scale Score Compared with Change in Function Tests

Correlation Coefficient

P Value

EILV/TLC Pesins/Pcapi/Vt/TLC% EELV/TLC RV/TLC Pesins/Pcapi FEV1 (% of predicted) SVC IC FVC% Trapped gas volume FEV1

0.749 0.544 0.390 0.259 0.185 0.072 0.069 0.063 0.056 0.047 0.034

⬍0.01 0.067 0.187 0.392 0.564 0.804 0.822 0.837 0.861 0.879 0.912

EELV ⫽ end-expiratory lung volume; EILV ⫽ end-inspiratory lung volume; FEV1 ⫽ forced expiratory volume in 1 second; FVC ⫽ forced vital capacity; IC ⫽ inspiratory capacity; Pcapi ⫽ maximal inspiratory muscle capacity; Pesins ⫽ inspiratory esophageal pressure; Pesins/Pcapi/Vt/ TLC% ⫽ index of neuroventilatory coupling for volume change; RV ⫽ residual volume; SVC ⫽ slow vital capacity; TLC ⫽ total lung capacity; Vt ⫽ tidal volume. Reprinted with permission from Am J Respir Crit Care Med.15

ASSESSMENT OF DYSPNEA IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE A discrepancy often exists between the patient’s perception and the physician’s clinical evaluation of the impact of symptoms that frequently accompany COPD, particularly as it relates to dyspnea. The patient’s individual perception of symptom burden frequently does not correspond precisely with the clinician’s assessment of traditional signs during physical examination, such as labored breathing, breath sounds and wheezing, accessory muscle use, or changes in respiratory rate. The American Thoracic Society (ATS) has stressed the importance of identifying patient self-reported or subjective assessment when evaluating the intensity of dyspnea and its impact on HRQOL. The ATS defines dyspnea as a subjective experience of breathing discomfort consisting of qualitatively distinct sensations that vary in intensity.6 According to the ATS, dyspnea arises “from interactions among multiple physiological, psychological, social, and environmental factors and may induce secondary psychological and behavioral responses.”6 Dyspnea is often associated with a change in the patient’s level of physical activity and is first reported in association with activities; then, as the disease progresses, it is also reported at rest. Patients with COPD frequently report dyspnea—and related symptoms of fear and anxiety—with everyday tasks, limiting activities of daily living. Therefore, it has been suggested that patients with COPD may be in a cycle of decline (dyspnea spiral) of symptom-induced inactivity, leading to deconditioning and muscle weakness.7,8 Pulmonary physiologic assessments, such as FEV1, have been used as surrogate markers for symptoms of disease severity, such as dyspnea.9 Despite some studies that showed a relation between dyspnea and measures of lung

function,3,10 –13 no single physiologic measurement (i.e., FEV1) can adequately reflect the consequences of dyspnea in patients with COPD. Furthermore, pulmonary rehabilitation has been shown to produce improvements in dyspnea without significant changes in lung function14; and in patients receiving a short-acting bronchodilator, changes in FEV1 (percentage of predicted) during exercise did not correlate with change in dyspnea (r ⫽ 0.072; P ⫽ 0.804). Several independent variables, including resting and dynamic lung volumes and pressures, were also measured in these patients. Results showed poor correlation between these indices and dyspnea (assessed by the Borg scale) with the exception of the change in the end-inspiratory lung volume/total lung capacity ratio (Table 1).15 One study that enrolled 227 patients with COPD (mean FEV1 41% of predicted), demonstrated that the cumulative survival rates at 5 years were significantly correlated with the level of dyspnea at study entry but not with the ATSdefined stage of COPD, which is based on FEV1.16 The investigators in this study concluded that dyspnea, along with airway obstruction, should be considered in evaluating mortality risk factors in patients with COPD. Thus, using FEV1 as a surrogate marker can be misleading. The variable nature of dyspnea diminishes the probability that any 1 measure of disease can provide a reliable index when evaluating the intensity of dyspnea and/or the benefits associated with treatment. Direct measurement of dyspnea and other aspects of HRQOL may provide better estimates of the impact of disease and treatment effects.9

INSTRUMENTS FOR DYSPNEA ASSESSMENT Because assessment and evaluation of dyspnea depend on subjective experience, the measurement of dyspnea can be

S14 difficult and must rely on patients’ self-reports for quantification of its intensity and impact. Instruments can be discriminative, measuring differences in the intensity of dyspnea between groups of individuals, or evaluative, measuring changes in dyspnea as an outcome of intervention or treatment. Ideally, instruments to evaluate dyspnea should be of clinical value as well as relevant. Both types of instruments, discriminative and evaluative, must have good documentation of traditional reliability and validity. In addition to demonstrating reliability and validity, evaluative tools must be able to measure responsiveness.7 The tools for evaluation or assessment of dyspnea should also be easy to administer and quantify. Patient questionnaires and symptom assessment scales are 2 basic approaches for assessing and evaluating dyspnea based on patient-reported symptoms. An important component of patient questionnaires used to evaluate dyspnea is the period over which the patient is asked to report dyspnea experiences. For example, patients may be asked to evaluate their current level of dyspnea or the level of dyspnea experienced over the preceding weeks or over another period of time. Questionnaires that do not restrict the questions to a current level of dyspnea do not capture rapid changes due to a specific treatment; however, they are more suited to identifying long-term changes. This can be easily explained by the fact that they are not bound by an immediate time frame, are subsequently less susceptible to daily variability, and can therefore reflect the effect of therapy over a longer period. Questionnaires can also involve various scaling methods, which are important to consider, particularly in relation to responsiveness. For example, instruments with fewer scaling categories available (e.g., a 4-point scale) may be less sensitive to quantify small but meaningful changes in dyspnea than are instruments with a greater number of scaling categories (e.g., a 10-point scale). Therefore, when selecting a dyspnea evaluation tool, scaling as well as question framing should be considered to ensure the instrument chosen is adequate for the purpose intended. On the basis of various characteristics, dyspnea assessment instruments may be grouped into 3 categories: (1) standardized questionnaires that require patients to recall dyspnea symptoms that occurred during activities of daily living over a previous period; (2) instruments that evaluate the patient’s current level of dyspnea; (3) HRQOL instruments that recognize the impact of dyspnea on patient HRQOL and, therefore, include a domain of dyspnea. Several instruments used to assess and evaluate dyspnea are reviewed here. Basic characteristics of these instruments are summarized in Table 2.

Instruments That Evaluate Dyspnea Over Time Medical Research Council (MRC) Scale. In use for several decades, the Medical Research Council (MRC) dyspnea scale evaluates the effect of breathlessness on daily activities. This instrument is easy to administer and correlates

The American Journal of Medicine, Vol 119 (10A), October 2006 well with patient self-reported complaints of dyspnea. The MRC scale can be used to complement FEV1 in the diagnosis of COPD.17 On the basis of their difficulty with normal daily activities, such as walking or climbing stairs, patients were originally categorized into 1 of 5 grades, ranging from grade 1 (“normal”) to grade 5 (“too breathless to leave the house)”.17 Subsequently, the ATS issued a revised 5-grade version of the MRC scale that ranges from grades 0 to 4 (Table 3).18 The revised scale focuses primarily on the dyspnea that occurs while walking. Typically, patients are asked to indicate the level of activity that produces dyspnea and, at follow-up visits, can be monitored to detect changes in dyspnea related to normal exertion.6 Because the MRC scale evaluates dyspnea only as related to specific activities, it does not provide a direct quantification of dyspnea intensity levels. In addition, the MRC scale may not easily detect changes in the level of dyspnea following a therapeutic intervention. In fact, for patients with moderate-to-severe COPD, MRC scores tend to congregate in a relatively small portion of the scale, between grades 3 and 4; thus, this scale may be insensitive to small but clinically important changes in symptoms. Baseline Dyspnea Index/Transition Dyspnea Index. The Baseline Dyspnea Index (BDI) assesses breathlessness at a single point in time.6 Developed as an interviewer-administered scale, the BDI evaluates 3 dimensions of dyspnea: functional impairment, or the degree to which activities of daily living are impaired; magnitude of effort, or the overall effort exerted to perform activities; and magnitude of task, or the level and extent to which individual tasks can be performed before dyspnea is noticed.19 The BDI rates the patient’s dyspnea in each of these dimensions on a scale from 0 (no impairment) to 4 (extraordinary or severe impairment). A companion scale, the Transition Dyspnea Index (TDI) is used to monitor changes from baseline over time and can be used to assess the impact of therapeutic interventions. The TDI assesses changes in dyspnea over time in the 3 BDI dimensions on a scale from ⫺3 to ⫹3.20 The BDI and TDI both rely on raters to assign patients to different levels of dyspnea and, as a result, variability between interviewers may introduce error and variability into the scoring process. New self-administered computerized versions of the BDI/TDI have been developed to overcome this difficulty.21 University of California–San Diego Shortness of Breath Questionnaire. A self-report scale originally developed as a clinical tool for screening patients for pulmonary rehabilitation, the University of California–San Diego Shortness of Breath Questionnaire (SOBQ) comprises 24 items that assess dyspnea over the preceding week.6 Patients are requested to rate their dyspnea when performing 21 different activities on a scale ranging from 0 (not at all) to 5 (maximal or unable to do because of breathlessness). In addition,

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Characteristics of instruments commonly used to measure dyspnea

Instrument

Type

Self- or InterviewerAdministered

MRC (ATS) BDI/TDI SOBQ Borg VAS CRQ SGRQ

Symptom recall Symptom recall Symptom recall Current symptom Current symptom HRQOL HRQOL

Interviewer Interviewer Self Self Self Interviewer Self

Approximate Time to Complete (min) ⬍1 5 5 ⬍1 ⬍1 20 15

ATS ⫽ American Thoracic Society scale; BDI ⫽ Baseline Dyspnea Index; Borg ⫽ Borg scale; CRQ ⫽ Chronic Respiratory Disease Questionnaire; HRQOL ⫽ health-related quality of life questionnaire; MRC ⫽ Medical Research Council scale; SGRQ ⫽ St. George’s Respiratory Questionnaire; SOBQ ⫽ Shortness of Breath Questionnaire; TDI ⫽ Transition Dyspnea Index; VAS ⫽ Visual Analog Scale.

Table 3 American Thoracic Society revision of the Medical Research Council dyspnea scale Grade

Degree

Comments

0

None

1

Slight

2

Moderate

3

Severe

4

Very severe

Not troubled with breathlessness except with strenuous exercise Troubled by shortness of breath when hurrying on the level or walking up a slight hill Walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level Stops for breath after walking about 100 yards or after a few minutes on the level Too breathless to leave the house or breathless when dressing or undressing

Reprinted from Am Rev Respir Dis.18

patients are requested to rate 3 additional questions related to limitations secondary to dyspnea, fear of harm from overexertion, and fear of shortness of breath; thus, the total score ranges from 0 to 120. The SOBQ displays good reliability and correlation with the 6-minute walk distance and FEV1, and it has been shown to be sensitive to improvements in dyspnea that occur during rehabilitation.20 Although the questionnaire can be easily self-administered by the patient, it is important that the clinician ensure that all questions have actually been answered. It is helpful to supervise the first administration to familiarize patients with the questionnaire and answer any questions they may have. For any activities they do not perform, patients are asked to estimate their level of dyspnea for that activity. One should also keep in mind that some patients may not have the reading skills necessary to complete the questionnaire ac-

curately and may need assistance, an uncontrolled factor that is not always easy to detect but that could affect validity.

Instruments That Evaluate the Patient’s Current Level of Dyspnea Perceived symptom rating scales reflect the patient’s current performance status, typically before, during, and after specific tasks such as exercise.20 In assessing dyspnea during exercise, 2 scales have been used widely: the Borg scale and the Visual Analog Scale (VAS). Borg Scale. Commonly used to examine the effects of exercise on dyspnea, the modified Borg scale is a logarithmic category-ratio scale. In 1971, Borg described a per-

S16 ceived exertion scale with ratings ranging from 6 to 20 that assessed “perceived exertion” during physical exercise (corresponding with a heart rate range of 60 to 200 beats per minute). This scale was subsequently modified to a 10-point scale and is used to rate various “perceived symptoms” such as dyspnea or muscle fatigue (Table 4).22,23 Care must be taken to provide consistent, specific instructions when using the Borg scale. For instance, different investigators have asked subjects to rate “severity of breathlessness,” “need to breathe,” and “effort of breathing,” variations that can elicit different responses. Further, it may be difficult to interpret some of the patient responses to this scale. For instance, what does “maximal” (rating of 10) mean to the patient? Does it refer to the worst breathlessness the patient could imagine or does it represent the worst breathlessness the patient has ever experienced? Despite these potential drawbacks, the reliability and validity of this measure have been established in the general population and in patients with COPD.20 VAS. The VAS typically consists of a 100-mm line anchored at either end with verbal descriptors that represent the extremes of sensation—for instance, maximal breathlessness at one extreme and no breathlessness at the other.6 Patients are instructed to mark the line at the point corresponding to their level of symptoms; the distance along the line is then measured. The VAS has been shown to be a reliable and valid measure not only of the sensation of dyspnea but also of the accompanying effort and distress.20

Health-Related Quality-of-Life Questionnaires That Include Assessment of Dyspnea Recently, the comprehensive assessment of dyspnea has expanded to encompass the evaluation of how cognition, beliefs, and behaviors that reflect the patient’s understanding of—and responses to—COPD act together to influence the patient’s day-to-day HRQOL.6 Essentially, HRQOL questionnaires that assess these variables evaluate dyspnea within the larger framework of how this disease interferes with the patient’s normal life. Chronic Respiratory Disease Questionnaire. The Chronic Respiratory Disease Questionnaire (CRQ) is a 20-item, disease-specific questionnaire that can be either intervieweradministered or self-administered. It comprises 20 items that evaluate 4 dimensions of COPD: dyspnea, fatigue, emotional function, and mastery.6,20 The total score of the CRQ quantifies the broader impact of COPD on the patient’s HRQOL, in which dyspnea represents one element among others. However, the dyspnea subscale of the CRQ can be considered on its own. The dyspnea component of this questionnaire asks the patient to identify 5 activities that induced a state of breathlessness within the last 2 weeks, with the severity of breathlessness evaluated on a 7-point scale, ranging from 1 (most dyspnea) to 7 (least dyspnea).6 However, the activities identified by each patient are unique

The American Journal of Medicine, Vol 119 (10A), October 2006 Table 4

Modified Borg scale: perceived breathlessness

Borg Scale Score

Definition

0 0.5 1 2 3 4 5 6 7 8 9 10

Nothing at all Very, very slight (just noticeable) Very slight Slight Moderate Somewhat severe Severe — Very severe — Very, very severe (almost maximal) Maximal

Adapted with permission from Med Sci Sports Exerc22 and Am Rev Respir Dis.23

to that patient, making it difficult to compare dyspnea scores obtained from different patients. St. George’s Respiratory Questionnaire. The St. George’s Respiratory Questionnaire (SGRQ) is a self-administered 76-item questionnaire that measures 3 domains: symptoms, activity, and impact of disease on daily life. In this questionnaire, dyspnea is not evaluated specifically; instead, it is included in the symptom scale, along with information about cough, sputum production, and wheezing.6

CHRONIC OBSTRUCTIVE PULMONARY DISEASE INTERVENTIONS THAT IMPROVE DYSPNEA Clinical trials of pulmonary rehabilitation and pharmacologic interventions, or a combination of both, have often included assessments of functional capacity, HRQOL, and dyspnea as important health outcomes in patients with COPD.

Pulmonary Rehabilitation Increasingly recognized as an integral component of a comprehensive COPD management program, pulmonary rehabilitation is directed at changing patients’ perceptions and tolerance of COPD symptoms and increasing functional capacity without necessarily improving pulmonary function.24 Fundamentally a multidisciplinary approach to COPD management, pulmonary rehabilitation combines education and exercise to stabilize or reverse functional limitations secondary to chronic lung disease.20 The primary goal of pulmonary rehabilitation is to restore the patient to the highest level of independent functioning, that is, to alleviate disability without necessarily changing the disease process itself.24,25 The American College of Chest Physicians (ACCP), in conjunction with the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR), have published evidenced-based guidelines for pulmonary rehabilitation that emphasize the importance of this treat-

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Figure 1 Results of treadmill exercise endurance tests for patients in the rehabilitation (Rehab) and education groups at baseline and during 12 months of follow-up as measured by changes in the Borg scale. Perceived breathlessness rating was made at the end of exercise. *P ⬍0.05 for within-group change from baseline; values and error bars represent the mean ⫾ SE. (Reprinted with permission from Ann Intern Med.14)

Figure 2 Self-reported shortness of breath with daily activities for patients in the rehabilitation (Rehab) and education groups at baseline and during 12 months of follow-up as measured by changes in the Shortness of Breath Questionnaire (SOBQ) scale. *P ⬍0.05 for within-group change from baseline; values and error bars represent the mean ⫾ SE. (Reprinted with permission from Ann Intern Med.14)

ment strategy in improving the symptoms of dyspnea, exercise tolerance, and HRQOL in patients with COPD.25 The ACCP/AACVPR guidelines consider lower- and upper-extremity training as indispensable components of pulmonary rehabilitation in COPD, with the use of ventilatory muscle training in selected patients with diminished respiratory muscle strength and breathlessness. The guidelines also promote the use of long-term educational and psychosocial interventions as beneficial steps in comprehensive pulmonary rehabilitation programs in COPD. Pulmonary rehabilitation has been shown to improve various measures of COPD symptoms and to lessen the impact of this disease on the patient’s daily functioning. For instance, with pulmonary rehabilitation in patients with severe to very severe COPD—FEV1 between 25% and 40% of predicted—typical findings comprise a 5- to

10-unit improvement on the SOBQ,26,27 a 2-unit improvement on the Borg scale,28,29 and approximately a 10-unit improvement on the VAS.30,31 A randomized, prospective clinical trial that included 119 outpatients with stable COPD compared the efficacy of comprehensive pulmonary rehabilitation with that of education alone.14 Pulmonary rehabilitation comprised twelve 4-hour sessions that included education, physical and respiratory care instruction, psychosocial support, and supervised exercise training. The education-only group attended four 2-hour sessions that included videotapes, lectures, and general discussions but no individualized instruction or exercise training. When compared with education alone, comprehensive pulmonary rehabilitation produced significantly greater reductions in dyspnea measured during exercise by the Borg scale and the SOBQ, with approximately 2- and

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Figure 3 Transitional Dyspnea Index (TDI) focal scores at days 57, 113, and 169 for the tiotropium, salmeterol, and placebo groups. *P ⬍0.05 for tiotropium vs. placebo. †P ⬍0.05 for tiotropium vs. salmeterol. (Reprinted with permission from Chest.35)

8-unit improvements, respectively, for the experimental group compared with the control group (Figures 1 and 2).14 The California Pulmonary Rehabilitation Collaborative Group also examined the effectiveness of pulmonary rehabilitation, as practiced in the general California medical community, as a means of reducing dyspnea symptoms and improving HRQOL.32 This 2-year, multicenter outcome study enrolled 542 patients with chronic lung disease (average FEV1 44% of predicted) who completed self-administered QOL questionnaires before and immediately after pulmonary rehabilitation as well as at 3, 6, 12, and 18 months after rehabilitation. The results revealed that pulmonary rehabilitation produced clinically meaningful initial and long-lasting reductions in SOBQ scores when compared with baseline.

Pharmacologic Interventions Bronchodilating agents can contribute to a reduction in dyspnea symptoms in selected populations of patients with COPD.6 For instance, anticholinergics and inhaled ␤2-agonists, as well as sustained-release theophylline, have been shown to improve the symptoms of dyspnea in patients with stable COPD.6 As a result, long-acting bronchodilators are recommended by the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines as central treatments for the symptomatic management of stable COPD.33 Tiotropium, a long-acting, once-daily inhaled anticholinergic, has demonstrated clinically significant benefits in the management of COPD, either in conjunction with pulmonary rehabilitation or as single-agent therapy. In a small, randomized, double-blind trial, tiotropium or placebo was administered once daily to 91 patients with

COPD (FEV1 34% of predicted) who were participating in an 8-week pulmonary rehabilitation program that consisted of treadmill training 3 times weekly.34 The results demonstrated that tiotropium, in combination with pulmonary rehabilitation, significantly improved treadmill-testing endurance and produced clinically relevant improvements in symptoms as measured by changes in SGRQ scores. The improvements associated with tiotropium were maintained during the 3 months after the pulmonary rehabilitation program was completed. In another randomized study, 643 patients with COPD (FEV1 40% of predicted) were randomly assigned to treatment with either 1 of 2 long-acting bronchodilators (tiotropium or salmeterol) or placebo for 6 months.35 Tiotropium treatment yielded significantly greater improvements in FEV1 when compared with salmeterol. Moreover, tiotropium treatment yielded significant improvements in TDI scores (1.02 units) when compared with placebo, while improvements with salmeterol treatment (0.24 units) were not statistically different from that with placebo (Figure 3).35 These findings were further supported by the results of a 12-month randomized trial that included 921 patients with COPD (FEV1 40% of predicted) who were treated with either tiotropium or placebo.36 In this study, statistically significant and clinically meaningful TDI score improvements of approximately 1 unit were noted with tiotropium treatment compared with placebo, and this improvement in dyspnea was sustained over the 12-month study (Figure 4).36 Several clinical studies with inhaled corticosteroids demonstrated improvements in dyspnea,37,38 whereas others have failed to show any benefit.39,40 A 3-month trial with

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Figure 4 Mean Transition Dyspnea Index (TDI) focal score at the 5 assessment points during the 1-year trial. (Top curve) tiotropium (n ⫽ 507); (bottom curve) placebo (n ⫽ 325). Data are presented as mean ⫾ SEM. Means were adjusted for treatment, center, and Baseline Dyspnea Index; a higher score denotes less dyspnea. *P ⬍0.001 vs. placebo. (Reprinted with permission from Eur Respir J.36)

fluticasone (440 ␮g bid) showed a small but statistically significant improvement in dyspnea (3.47 ⫾ 0.19 for placebo vs. 3.70 ⫾ 0.18 for fluticasone; P ⫽ 0.03) on the CRQ scale.38 Similarly, a 36-month study showed a decrease in dyspnea with triamcinolone compared with placebo (P ⬍0.02); 68.2% of patients receiving triamcinolone had no dyspnea compared with 61.5% of placebo recipients.37 In contrast, another trial with high-dose fluticasone showed no improvement in dyspnea after 6 months compared with placebo39; moreover, in a 3-year trial with budesonide, no significant difference in dyspnea was noted between budesonide treatment and placebo.41 Trials using the 2 fixed-dose combinations of fluticasone-salmeterol (fluticasone 250 ␮g–salmeterol 50 ␮g and fluticasone 500 ␮g–salmeterol 50 ␮g) showed significant improvement in dyspnea compared with placebo.42– 44 More recently, it has also been shown that the fixed-dose combination of fluticasone-salmeterol (fluticasone 250 ␮g–salmeterol 50 ␮g bid) improved dyspnea from baseline compared with ipratropium-albuterol (ipratropium 36 ␮g–albuterol 206 ␮g qid). After 8 weeks, the mean TDI score was 2.7 ⫾ 0.2 above baseline (P ⱕ0.05) and the percentage of patients achieving a TDI score ⱖ1 was 64% (vs. 44% for ipratropium/albuterol; P ⬍0.001).45

SUMMARY Increasingly recognized as an important contributor to the disability associated with COPD, dyspnea provides information about the impact of respiratory impairment on the patient’s HRQOL, likely the most important aspect of COPD from the patient’s perspective. No longer solely an outcome measure in clinical research of chronic lung disease, dyspnea is increasingly—and appropriately— considered a fundamental, and potentially modifiable, symptom of

COPD in the clinical setting. Indeed, in patients with COPD, any of the instruments that measure dyspnea in an organized, systematic, and simple-to-use manner (i.e., the MRC questionnaire or the VAS) could be incorporated into clinical practice to detect dyspnea-related disability, assess changes in function over time, or gauge the benefits of treatment. Yet, in the primary care setting, even a few simple questions related to the presence and extent of dyspnea may yield substantial diagnostic and prognostic information. For instance, asking the patient, “Can you walk 100 yards?” or “Does breathlessness prevent you from leaving the house?” can yield clinical insight into the practical limitations currently imposed by dyspnea, providing an opportunity for further evaluation and intervention. Among the interventions that have demonstrated the ability to reduce dyspnea are pulmonary rehabilitation and pharmacologic treatment, or the combination of both. The GOLD guidelines recommend the regular use of bronchodilators, preferably long-acting bronchodilators, as the primary maintenance treatment for COPD. The effects of inhaled corticosteroids on dyspnea have not been consistent and are generally recommended for patients with severe COPD and frequent exacerbations only.

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