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Am JRespir Crit Care Med Vol 158. pp 11851189, 1998Internet address: www.atsjournals.org

Analysis of Clinical Methods Used to Evaluate Dyspneain Patients with Chronic Obstructive Pulmonary Disease

TAKASHI HAJIRO, KOICHI NISHIMURA, MITSUHIRO TSUKINO, AKIHIKO IKEDA,HIROSHI KOYAMA, and TAKATERU IZUMI

Department of Respiratory M edicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan

When dyspnea must be assessed clinically, there are three methods of assessment: the measurement

of dyspnea with activities of daily living using clinical dyspnea ratings such as the modified M edical

Research Council (M RC), the Baseline Dyspnea Index (BDI) , and the Oxygen Cost Diagram (OCD);

the measurement of dyspnea during exercise using the Borg scale; to assess the influence of dys-

pnea on health-related quality of life (HRQoL) using disease-specific questionnaires such as the St.

Georges Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Disease Questionnaire

(CRQ). The purpose of the present cross-sectional study was to clarify relationships between dyspnea

ratings and HRQoL questionnaires by applying factor analysis. One hundred sixty-one patients with

mild to severe COPD completed pulmonary function tests, progressive cycle ergometer testing for

exercise capacity, assessment of dyspnea, HRQoL, anxiety, and depression. Factor analysis demon-

strated that the MRC, BDI, OCD, and Activity of the SGRQ, and Dyspnea of the CRQ, were grouped

into the same factor, and the frequency distribution histograms of these five measures showed virtu-ally the same distribution. The Borg scale at the end of maximum exercise was found to be a different

factor. The MRC, BDI, OCD, and Activity in the SGRQ, and Dyspnea in the CRQ demonstrated the

same pattern of correlation with physiologic data, and they had significant relationships with FEV1(correlation coefficients [Rs] 0.31 to 0.48) and maximal oxygen uptake (Rs

0.46 to 0.60) . Disease-

specific HRQoL questionnaires, the SGRQ and the CRQ, which contain a specific dimension for evalu-

ating dyspnea, may be substituted for clinical dyspnea ratings in a cross-sectional assessment. Dys-

pnea rating at the end of exercise may provide further information regarding dyspnea. Hajiro T,

Nishimura K, Tsukino M, Ikeda A, Koyama H, Izumi T. Analysis of clinical methods used to

evaluate dyspnea in patients with chronic obstructive pulmonary disease.

AM JRESPIR CRIT CARE MED 199 8;158 :1185 1189.

The evaluation of dyspnea in patients with COPD should beincluded among standard measures of physiologic lung func-

tion since dyspnea ratings and lung function are separate fac-

tors that independently characterize the condition of pat ientswith COPD (1). Dyspnea with activities of daily living (ADL)

has been measured using clinical dyspnea ra tings such as thoseof the modified Medical Research Council (MRC) (2), the

Baseline D yspnea Index (BD I) (3), and the O xygen Cost Dia-gram (O CD ) (4), all of which have been widely used. Dyspnea

during exercise testing or with physical activity has been mea-sured with the Borg scale (5), or the V isual A nalog Scale (6).

Arbitrary choices on the dyspnea scale have been made inclinical trials when clinical evaluation of dyspnea was utilized

as one of the out come measures.

On the other hand, an important aim of medical interven-

tions may be to improve no t only the quan tity of life but alsothe quality of life of each patient. Because the term health-

related quality of life (HRQoL) is widely used to describehow the quality of life of patients is affected by health and dis-

ease status, a well-designed HR QoL questionnaire should en-compass comprehensive dimensions that quantify the overall

effect of disease on the patien ts daily life and sense of well be-ing (7, 8). In patients with COPD, it is essential for a measure

of HR QoL to include an assessment of influences attributableto dyspnea. Disease-specific questionnaires for COPD have a

specific dimension in which the impacts of dyspnea on patient

health status are supposed to be evaluated (8, 9).Presently there are three possible ways to assess dyspnea

clinically: the measurement of dyspnea during ADLs usingclinical dyspnea ratings, the measurement of dyspnea during

exercise testing in laboratories using dyspnea ratings, and theassessment of the influence of dyspnea on H RQ oL using a dis-

ease-specific questionnaire. We speculate that a disease-spe-cific HRQoL questionnaire can evaluate dyspnea as well as

clinical dyspnea ratings can. The purpose of the present cross-sectional study was to clarify interrelationships between clini-

(

Received in original form February 19, 1998 and in revised form June 11, 1998

)

Correspondence and requests for reprints should be addressed to Takashi Hajiro,M.D., Department of Respiratory Medicine, Graduate School of Medicine, Kyoto

University, Sakyo, Kyoto, 606-8507, Japan. E-mail: [email protected] o-u.ac.jp


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AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 158 1998

cal dyspnea ratings, dyspnea ratings at maximal exercise, and

HR QoL questionnaires by applying factor analysis (10), andto clarify the suitability of evaluating patient dyspneic status

using the various methods.

METHODS

Patients with stable CO PD defined by the A merican Thoracic Society

(11) were recruited at the out patient clinic. All patients had more tha n

6 mo of outpatient management before entry to avoid substantial

changes in subjective parameters brought about by new medical inter-

ventions (12). Entry criteria for the study were: (

1

) a FEV

1

/FVC ratio

of less than 0.7 and FEV

1

of less than 80% of the predicted value for

all measurements made during the previous 6 mo; (

2

) smoking history

of more than 20 pack-yr; (

3

) no history suggestive of asthma; (

4

) no

exacerbation of airflow limitation in the preceding 6 wk; and (

5

) no

changes in treatment regimen during the preceding 4 wk. All eligible

patients underwent the following examinations on the same day.

Inhalation of bronchodilators was withheld for at least 12 h before

pulmonary function tests were performed. FEV

1

and FVC were as-

sessed before and 60 min after the inhalation of 400

g of salbutamol

and 80

g of ipratropium bromide using a metered-dose inhaler with a

spacer device (InspirEase; Schering-Plough K.K, Osaka, Japan). All

spirometric flowvolume curves were recorded according to the

method described in the American Thoracic Society 1994 update (13).

The predicted values for FEV

1

and vital capacity (VC) were calcu-

lated according to the proposal of the Japan Society of Chest Diseases

(14). The residual volume (RV) was measured by the closed-circuit

helium method and the diffusion capacity for carbon monoxide

(D

LCO

) was measured using the single-breath technique (CH ESTAC-

65V; Chest, Tokyo, Japan). The progressive exercise test to a symp-

tom-limited maximum was performed using an electrically braked cy-

cle ergometer (Corival WLP-400; Lode, Groningen, The Netherlands)

at 60 min after the inhalation of the bronchodilators as described by

Ikeda and colleagues (15). The workload was increased automatically,

and patients maintained a pedaling frequency above 40 cycles/min

throughout the test. Exercise data were re corded using an automated

exercise testing system (Desktop Diagnostics/CPX; Medical Graphic

Corp., St. Paul, MN). At the end of each exercise test, maximum oxy-

gen uptake (

O2

max) was calculated and breathlessness was scored

with the Bo rg scale (0 to 10) (5).

To assess dyspnea, the Japanese version of the modified MRC (2),the BD I (3, 16), and the OCD (4) were used. The MR C is a five-point

scale based on degrees of various physical activities that precipitate

dyspnea. The BD I recognizes five grades for each o f the following cat-

egories: functional impairment, magnitude of task, and magnitude of

effort. The OCD is a visual analog scale that corresponds to oxygen

requirements at different activity levels, which was represented as a

value ranging from zero to 100, with a score of 100 indicating no im-

pairment. The HRQoL was assessed by the Japanese version of the

St. Georges Respiratory Questionnaire (SGRQ ) (8) and the Chronic

Respiratory Questionnaire (CRQ) (9), which have been precisely val-

idated (17). The SGRQ has three dimensions: Symptoms, concerned

with respiratory symptoms; Activity, concerned with activities that

evoke or are limited by dyspnea; and Impacts, a measure of the over-

all disturbance. The CR Q has four components: Dyspnea, E motional

Function, Mastery, and Fatigue. In the Dyspnea dimension, each pa-

tient defined the five items in terms of ADL limited by disease. TheJapanese version of the Hospital Anxiety and Depression Scale (HAD )

(18) was used for evaluating patients anxiety and depression status.

All results are presented as mean

SD. The relationship between

two sets of data was analyzed by Spearmans rank correlation test. A

p value of less than 0.01 was considered to b e stat istically significant.

Factor analyses was used to determine the dimensions underlying

the pa ttern of interrelationships and t o reduce a large set of variables

to smaller sets of factors (10). Factor analysis may be regarded as a

data reduction technique. In factor analysis, a matrix of correlations

between variables is created, and the n data are tran sformed into lin-

ear combinations of variables that share common variance between

measures. The correlations between the original variables and the lin-

ear combinations or factors are called factor loadings. By examining

which variables loaded highly on each factor, the factors were inter-

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preted and named. We incorporated the following variables in this

factor analysis: MRC, BDI, OCD, the Borg scale, three dimensions of

the SGRQ, the four components of the CRQ, and Anxiety and De-

pression of the HA D.

RESULTS

A total of 161 consecutive patients (160 men) with mild to se-vere COPD, and having a wide range of FEV

1

predicted val-

ues, were studied (Table 1). One hundred fifty-seven pa tients

were treate d with inhalation of both 400

g of salbutamol and80

g of ipratropium bromide more than four times a day.Seven patients were managed with long-term domiciliary oxy-

gen therapy. Four pa tients received no medication.

A summary of the varimax rotation of the factor a nalysis isprovided in Table 2. Three factors accounted for 70.0% of the

total variance of the data. The MRC, the BDI, the OCD, Ac-tivity in the SGR Q, and D yspnea in the CR Q loaded pred om-

inantly on Factor 1, which appeared to be the

dyspnea

fac-tor. Factor 2 included scores of anxiety and depression on t he

HAD, and appeared to be related to psychological status.Symptoms in the SGRQ and Fatigue, Emotion, and Mastery

in the CRQ loaded predominantly on Factor 3. Using theBorg scale, however, the dyspnea rating after maximal exercise

was found not to be grouped with any of the factors above. On

the basis of these results, we focused on Factor 1, the

dys-pnea

factor, in which the MRC, the BDI, the OCD, Activityin the SGR Q, and Dyspnea in the CRQ were grouped.

The frequency distribution histograms of the MRC, the

BDI, the OCD, Activity in the SGRQ, and Dyspnea in theCRQ are represented in Figure 1. These histograms demon-

strated virtually normal distributions.

TABLE 1

PATIENT CHARACTERISTICS IN 161 PATIENTS WITH COPD

Mean

SD Range

Sex, M/F 160/1

Age, yr 69

7 4889FEV

1

, L 1.06

0.49 0.172.65

FEV

1

, % pred 40.0

17.5 6079.8

Postbronchodilator FEV

1

, % pred 47.9

17.4 15.787.6

RV/TLC, % 46.9

10.3 26.171.2

D

LCO

, % pred 65.1

19.5 30.5131.2

Clinical dyspnea ratings

MRC score (04) 1.0 0.8 04

BDI score (012) 7.9 2.6 212

OCD (0100), mm 62 19 8100

Exercise test

O2

max, mL/min 829

270 2021,625

Borg score at the end of exercise 6.0

1.5 310

HAD

Anxiety (021) 3.9

3.3 017

Depression (021) 5.0

3.7 016

HRQoL questionnaires

SGRQ

Symptoms (0100) 52.5

19.9 7.8100

Activity (0100) 47.5

21.9 0100

Impact (0100) 25.7

16.9 075.6

CRQ

Dyspnea (535) 26.2

5.7 1135

Fatigue (428) 19.8

5.0 428

Emotional function (749) 39.5

7.0 1949

Mastery (428) 22.0

4.3 1128

Definition of abbreviations

: RV

residual volume; MRC

Medical Research Council;

BDI

Baseline Dyspnea Index; OCD

Oxygen Cost Diagram; O

2

max

maximum

oxygen up take; HAD

Hospital Anxiety and Depression Scale; HRQoL

health-related

quality of life; SGRQ

St. Georges Respiratory Questionnaire; CRQ Chronic Respira-

tory Disease Questionnaire.

* Numbers in parentheses represent the theoretical score range.

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: Dyspnea and Health-related Quality of Life 1187

Correlations between dyspnea ratings, HR QoL, and physi-ological data are shown in Table 3. Selected physiological vari-

ables were FEV

1

, RV/TLC, and O2

max representing airflowlimitation, hyperinflation, and exercise capacity, respectively.

The MRC, the BDI, the OCD, Activity in the SGRQ, andDyspnea in the CRQ displayed an almost identical pattern in

correlations with physiologic data. All of these had significantrelationships with FE V

1

(correlation coefficient [Rs]

0.31 to

V

0.48), and the O CD showed the strongest correlation. Measure-

ment of O2

max were correlated significantly with the

dys-

pnea

factor (Rs

0.46 to 0.60). There were no significant

correlations between RV/TLC a nd the BD I or Dyspnea in theCRQ. In contrast, the Borg scale at the end of exercise had no

significant relationship with FEV

1

, RV/TLC, or O2

max.

DISCUSSION

This cross-sectional study showed that factor a nalysis grouped

clinical dyspnea ratings (the MRC, the BDI, and the OCD)and two dimensions of the disease-specific HR QoL question-

naires under the same factor, and these five measures per-formed almost the same in assessing dyspnea in patients with

COPD. The Borg scale was found to evaluate a different as-pect of dyspnea using the methods mentioned above. HR QoL

questionnaires that contain a specific dimension for evaluatingdyspnea may be substituted for clinical dyspnea ratings in a

cross-sectional assessment.The factors grouped by factor analysis facilitated the selec-

tion of individual variables that may most closely representthe conceptual mean ing of the composite variable (10). In the

present study, it is reasonable to suppose that the MRC, theBDI, the OCD, Activity of the SGRQ, and Dyspnea of the

CRQ, which constituted Factor 1, have the same conceptualmeaning in common. These five methods may evaluate thesame aspect of dyspnea even though different approaches are

taken in each method to quantify dyspnea. The BDI and D ys-pnea of the CRQ present questions regarding the level of dys-

pnea that is provoked by patients ADL, and unidimensionalmeasures (the MRC, the OCD) de tect the threshold of activities

that bring physical limitations caused by breathlessness (16). In

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TABLE 2

ROTATED FACTOR LOADINGS FROM FACTOR ANALYSISIN 161 PATIENTS WITH COPD

Factor 1 Factor 2 Factor 3

Factor 1: dyspnea

MRC 1.00

0.10 0.23

BDI

0.85 0.05 0.07

OCD

0.92 0.11

0.24

Activity, SGRQ 0.81

0.06 0.17

Dyspnea, CRQ

0.55 0.12 0.34Factor 2: psychological status

Anxiety, HAD 0.00 0.91 0.00

Depression, HAD 0.15 0.86 0.00

Factor 3: other HRQoL

Symptoms, SGRQ 0.28

0.23

0.66

Fatigue, CRQ

0.15

0.17 0.66

Emotional function, CRQ 0.00

0.35 0.70

Mastery, CRQ 0.06

0.21 0.73

Other factors

Impact, SGRQ 0.47

0.06

0.44

Borg score at the end of the exercise 0.00 0.00 0.00

For definition of abbreviations, see

Table 1.

Figure 1. Frequency distribution histograms represent the scores of dyspnea assessments. In the MedicalResearch Council (MRC) and Activity of the St. Georges Respiratory Questionnaire (SGRQ), higher scoresindicate more severe dyspnea. In the Baseline Dyspnea Index (BDI), the Oxygen Cost Diagram (OCD),and the Chronic Respiratory Disease Questionnare (CRQ), higher scores indicate less impairment. Num-bers in parentheses represent the theoretical score range.


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Activity of the SGR Q (8), patients were asked to indicate withyes-no answers whether or not activities such as sitting, walk-

ing, or playing sports usually make them feel breath less.Add itionally, score distributions showed that the MR C, the

BDI, the OCD, Activity of the SGRQ, and Dyspnea of theCRQ have almost the same level of discriminatory power in

accordance with a wide range of disease severity despite dif-

ferences in the number of items, grading scales, and scoring ofeach method. Dyspnea of the CRQ (9) was developed as an

evaluative and not as a discriminative measure because pa-tients quantify their dyspnea during five self-selected activities

and the score in this dimension is individualized. However,our study showed that D yspnea in the CRQ was also discrimi-

native. With regard to the relationships of these methods withphysiologic parameters, expected information was obtained

such as mild correlations with airflow limitation and moder-ate-to-strong correlations with exercise capacity (19, 20). These

correlations further demonstrated minor differences, and this

suggests that these five measures may be similar in the valid-ity. These observations can lead us to suppose that arbitrary

choices of measures within the

dyspnea

factor, that is, the

MRC, the BDI, the OCD, Activity of the SGRQ, and Dys-

pnea of the CRQ may not make any significant difference when

clinical cross-sectional assessment for dyspnea is mandatory.The statistical method of factor analysis has been used pr e-viously to clarify the relationships between various parame-

ters in patients with CO PD, and our results partly support t hefindings of previous studies. Mahler and Harver (1) demon-

strated that clinical dyspnea ratings consisted of an indepen-dent factor, using principal-componen t factor ana lysis, although

they did not evaluate patients with an HRQoL questionnaire.Wegner and colleagues (20) also used factor analysis in patients

with moderate-to-severe COPD and demonstrated that dys-pnea ratings (the MR C, the OCD , and the BDI) and quality of

life evaluated with the CR Q re presented one independent en-

tity. It is not clear from their analysis how Dyspnea in theCRQ and the other t hree dimensions correlated with dyspnea

ratings and other parameters because they adopted the totalscore of t he CR Q in their analysis instead of the scores of the

four separate dimensions. In fact, Fatigue, Emotional Func-tion, and Mastery of the CRQ were grouped as a different fac-

tor from the

dyspnea

factor in the pre sent study. Incorporat-ing each dimension of the HRQoL questionnaires separately

into factor analysis may be mor e appr opriate in pr oviding in-sight into interrelationships between clinical dyspnea ratings

and HRQ oL.It is of interest to note that the Borg scale at the end of

symptom-limited exercise was found to be a completely sepa-rate entity in this factor analysis. This suggests that the Borg

scale may evaluate a different aspect of dyspnea from thatevaluated by other dyspnea r atings. The re asons for this may

be as follows: the intensity of an exercise task as measured by

the ergometer does not reflect patients A DL since they tendto avoid strenuous exercise in their daily life once they recog-

nize it causes dyspnea; lower-extremity symptoms can limitexercise performance and affect the sensation of dyspnea as

Mahler and Harver (21) demonstrated; the Borg scale is de-scribed as a direct measure since the patients are asked to

score sensations while they are actually experiencing dyspnea,

whereas patients reflecting on their daily life answer clinicaldyspnea ra tings indirectly (22).

The present study has some limitations. First, the cross-sec-tional analysis does not address the responsiveness of each

measure over time. Second, because our study included pre-dominantly men, generalization of t he r esults to women with

COPD may be uncertain.In conclusion, clinical dyspnea ratings (the MRC, the BDI,

the OCD) and Activity of the SGRQ and Dyspnea of theCRQ were grouped under the same factor, and these five

methods performed virtually identically in evaluating dyspneain patients with COPD . On the other han d, dyspnea at the end

of maximal exercise may provide a different type of informa-

tion regarding dyspnea. Disease-specific HRQoL question-naires may be substituted for clinical dyspnea ratings in the

cross-sectional assessment. Taken in the light of the growing

prevalence of HRQoL and its questionnaires as one measureof outcome, these observations may afford another perspec-tive on the measurement of dyspnea in clinical trials.

References

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TABLE 3

SPEARMANS RANK CORRELATIONS BETWEEN DYSPNEARATINGS, HRQoL, AND PHYSIOLOGICAL VARIABLES

IN 161 PATIENTS WITH COPD

MRC BDI OCD Activity, SGRQ Dyspnea, CRQ

FEV

1

0.39 0.31 0.48

0.36 0.35

RV/TLC 0.23

0.14*

0.31 0.25

0.19*

O2

max

0.60 0.46 0.56

0.55 0.46

For definition of abbreviations, see

Table 1.

All values listed represent statistically significant relationships (p

0.01) except thetwo values indicated w ith asterisks.

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