(Chest. 2000;117:54S-57S.)
© 2000
American College of Chest Physicians
How Should Health-Related Quality of Life Be Assessed in Patients With COPD?*
Donald A. Mahler, MD, FCCP
*
From the Section of Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH.
Correspondence to: Donald A. Mahler, MD, FCCP, Dartmouth Medical School, Section of Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH 03756-0001; e-mail: Donald.a.mahler{at}hitchcock.org
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Abstract
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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
ß2-agonist, anticholinergic, and theophylline medications
can improve HRQOL, as compared with placebo therapy.
Key Words: bronchodilator therapy • disease-specific instrument • dyspnea • generic health measure • minimum clinically significant change
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Introduction
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Health
-related quality of life (HRQOL) refers to the physical, psychological,
and social domains of health that are unique to each
individual.1
Each of these domains can be measured by the
objective assessments of functioning or health status and the
subjective perceptions of health. Other valued aspects of life exist
that are not generally considered as "health," including income,
freedom, and the environment.2
Interest in HRQOL over the past decade has increased
substantially because of recognition of the following factors: (1)
individual patients are most concerned about their symptoms
(eg, dyspnea) and their function (eg, ability to
perform physical tasks), rather than objective measures such as
expiratory airflow; (2) HRQOL is a unique construct that is different
from physiologic measures or survival3
; and (3) the goals
of therapy have been expanded to include relief of symptoms and
improvement in HRQOL in addition to the standard physiologic
outcomes.4
5
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Types of Instruments to Measure HRQOL
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These instruments were designed to provide a standardized
method by which health status or levels of health impairment could be
measured and compared in individual patients as well as in groups of
patients. There are three distinct types of instruments to measure
HRQOL.2
Utility Scale
This type of instrument attempts to quantify different
states of health on a continuum from perfect health (one anchor) to
death (another anchor). This approach is particularly valuable to
health economists.
General or Generic Health Measures
These instruments quantify a wide range of diseases and disease
states and are anchored at one end by perfect health and at the other
end by the worst possible health. Examples include the Sickness Impact
Profile,6
the Short-Form 36-item questionnaire
(SF-36),7
and the Nottingham Health Profile.8
Although such measures can provide valid estimates of impaired health
in chronic respiratory disease, this approach appears to be relatively
insensitive to detect small changes in response to a therapeutic
intervention.
Disease-Specific Measures
These questionnaires were developed to consider the major or key
components that influence the specific disease. In patients with COPD,
Guyatt et al4
reported that dyspnea, fatigue, emotional
function, and mastery were the major concerns of patients and are
measured as four components in the Chronic Respiratory Questionnaire
(CRQ); Jones et al9
proposed that symptoms, activity, and
impacts were the important constructs as included in the St. George’s
Respiratory Questionnaire (SGRQ); and Tu et al10
incorporated the dimensions of physical function, emotional function,
coping skills, and treatment satisfaction in the Seattle Obstructive
Lung Disease Questionnaire (SOLQ).
The characteristics of selected general and disease-specific
questionnaires for measuring HRQOL in patients with COPD are listed in
Table 1 .
Harper et al11
compared results from both generic (SF-36
and the Eurocol Classification of Health) and disease-specific (CRQ and
SGRQ) instruments with physiologic measurements in patients with COPD
at baseline and at follow-up at 6 months and 12 months. Based on
comparative analyses, they concluded that the SF-36 was superior to the
Eurocol Classification of Health and that the CRQ performed slightly
better than the SGRQ.
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Why Measure HRQOL?
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One important reason for measuring HRQOL in patients with
chronic respiratory disease is to differentiate between patients who
have a better health status and those who have a worse health status (a
discriminative instrument). For example, Mahler et al12
showed that patients with symptomatic COPD had lower scores for HRQOL
compared with all patients evaluated by one of 536 primary care
physicians or specialists (Fig 1)
.13
Furthermore, Hajiro et al14
and Mahler
and Mackowiak15
found that patients with COPD who reported
more severe dyspnea and exhibited more impaired lung function had, in
general, lower scores for HRQOL. Ferrer et al16
reported
that different stages of COPD based on the FEV1
percent of predicted separated groups of patients with varying degrees
of impairment in HRQOL using the SGRQ. Even patients with stage I
disease (FEV1 
50% predicted) had lower
values for HRQOL compared with a normal population.16
17
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Figure 1.. Group mean values for health components on the
Medical Outcomes Study 20-item questionnaire in 11,186 patients who
visited a primary care physician or a specialist,13
compared with 110 patients with symptomatic COPD.12
Patients with COPD had substantially lower values for physical and role
functioning as well as health perceptions compared with a general
patient population.
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The most widely used application (for both clinical and research
purposes) for measuring HRQOL is to detect how much HRQOL has changed
in response to therapy (an evaluative instrument). The responsiveness
of an evaluative instrument is an essential criterion to evaluate the
impact/benefit of a specific intervention on the outcome of health
status. Related to the responsiveness criterion of a HRQOL
questionnaire is the threshold for a clinically meaningful change. A
minimum clinically significant change (MCSC) has been established for
some HRQOL instruments in order to indicate the relative value of any
measured change in health status and to guide the interpretation as to
whether the change in scores is "clinically
meaningful."18
The proposed values for a MCSC are as
follows: a change of at least 4 points in the overall score for the
SGRQ9
; a change of approximately 5 points on the
SOLQ10
; and a change of at least 10 points for the
CRQ.4
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HRQOL as an Outcome Measure for Evaluating Pharmaceutical Therapy
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ß2-Agonist Therapy
Guyatt et al19
reported that salbutamol, 200 µg
qid, improved dyspnea, physical function, and emotional function
(components of the CRQ), as well as lung function and walking distance
compared with placebo therapy, 2 puffs qid, over 2 weeks in 19 patients
with symptomatic COPD. Jones and Bosh20
evaluated changes
in the SGRQ in patients with COPD treated with placebo (n = 95);
salmeterol, 50 µg bid (n = 94); and salmeterol, 100 µg bid
(n = 94), for 16 weeks. Compared with placebo, the 50 µg dose of
salmeterol provided significant improvements in the "Total" and
"Impacts" scores of the SGRQ that exceeded the threshold for a
clinically significant change. The absence of any significant
improvement in HRQOL with the 100 µg dose of salmeterol may have been
related to side effects such as tremor and central nervous stimulation.
Comparison of ß2-Agonist and Anticholinergic
Medications
Van Schayck et al17
reported no significant
differences in changes in the Nottingham Health Profile between
salbutamol, 400 µg qd, and ipratropium, 160 µg qd, over a 2-year
period in 93 patients with mild COPD (FEV1
50% predicted). However, the authors commented that a
disease-specific HRQOL instrument might have been more sensitive to
detect an improvement in health status.
In a 12-week, multicenter trial of 411 patients with COPD
(FEV1 
65% predicted), Mahler et
al21
found that groups who received salmeterol, 42 µg
bid, or ipratropium bromide, 36 µg qid, had higher overall scores
(improvement) on the CRQ compared with placebo therapy, 2 puffs qid
(Fig 2)
.
Furthermore, the proportion of patients who achieved an increase of
10 points (the MCSC) in the total score was significantly higher
for salmeterol (46%; p = 0.007) and ipratropium (39%; p = 0.041)
groups compared with the placebo group (27%). There were also greater
improvements in the clinical ratings of dyspnea (the Transition Dyspnea
Index) over the study period in patients treated with salmeterol or
ipratropium compared with placebo.
Theophylline
Several studies have demonstrated that theophylline improves
dyspnea in patients with moderate to severe COPD compared with placebo
therapy.19
22
23
However, a more relevant clinical
question is whether theophylline provides further benefit when added to
inhaled bronchodilator therapy.
McKay et al24
examined the addition of theophylline to
inhaled ß2-agonist and ipratropium therapy in
15 patients with severe COPD (FEV1 31 ± 15%
predicted). Although there were no significant changes in
FEV1 or FVC with theophylline compared with
placebo, patients experienced significant improvements in dyspnea (mean
change, 15 points) and reductions in fatigue (mean change, 9 points) on
the CRQ with high-dose therapy (theophylline level of 16.8 ± 4.2
mg/L). However, there were no differences in emotional and mastery
scores compared with placebo therapy.
Mahon et al25
studied 68 patients with "irreversible"
COPD who were able to tolerate theophylline and were uncertain as to
whether previous use of theophylline was beneficial. One half of the
patients received standard therapy (patients stopped taking
theophylline but resumed it if their dyspnea worsened), while the other
34 patients received an "n of 1" trial (randomized, double-blind,
multiple crossover comparisons of theophylline and placebo treatments
in a single patient). Although there were no differences in the CRQ
scores between groups over 1 year, the investigators reported that 21%
of patients in the n of 1 trial showed improvement in dyspnea with
theophylline.
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Summary
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HRQOL has become an established outcome measure for evaluating the
efficacy of therapeutic interventions, particularly bronchodilator
medications, in patients with COPD. Both patients and physicians find
the items of a disease-specific instrument more relevant to the
individual’s medical problems. Also, these questionnaires are more
responsive and therefore have greater potential to demonstrate a
significant and meaningful change.5
With a generic
instrument, previously unrecognized adverse effects may be detected and
comparisons can be made across patient populations.
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Footnotes
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Abbreviations: CRQ = Chronic
Respiratory Questionnaire; HRQOL = health-related quality of life;
MCSC = minimum clinically significant change; SF-36 = Short-Form
36-item questionnaire; SGRQ = St. George’s Respiratory
Questionnaire; SOLQ = Seattle Obstructive Lung Disease Questionnaire
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TOP
Abstract
Introduction
CRQ) after 12 weeks of treatment with salmeterol
(n = 135), ipratropium bromide (n = 135), or placebo (n = 143) in
patients with COPD (FEV1