Arthritis & Rheumatism (Arthritis Care & Research)

Vol. 59, No. 4, April 15, 2008, pp 537545

DOI 10.1002/art.23534
2008, American College of Rheumatology

ORIGINAL ARTICLE

Fitness, Fatigue, Disease Activity, and Quality of

Life in Pediatric Lupus
KRISTIN M. HOUGHTON,1 LORI B. TUCKER,1 JAMES E. POTTS,1

AND

DONALD C. MCKENZIE2

Objective. To measure aerobic tness (maximum oxygen consumption [VO2peak]), fatigue, quality of life (QOL), and
disease activity in young persons with systemic lupus erythematosus (SLE), and to determine an equation for predicting
VO2peak from the distance walked in 6 minutes (6MW).
Methods. Fifteen young patients ages 1219 years with SLE participated. VO2 was measured by a graded treadmill
exercise test. Submaximal exercise intensity was determined from the ventilatory anaerobic threshold. Submaximal
aerobic capacity was measured using the 6MW. Patient questionnaires included measures of fatigue, QOL, and physical
activity. Physician questionnaires included the Systemic Lupus Erythematosus Disease Activity Index and the Systemic
Lupus International Collaborating Clinics/American College of Rheumatology Damage Index.
Results. Compared with age-matched norms, our patients had moderate impairment in aerobic tness, with a mean SD
VO2peak of 31.1 7.9 ml/minute/kg and a mean 6MW distance Z score of 2.4 2.3. The regression equation to predict
VO2peak (ml/minute/kg) from 6MW was as follows: 57.1 [0.038 distance (meters)] (0.35 maximal heart rate) (R
0.67, P 0.027). Ten subjects (67%) reported signicant fatigue. There was no signicant correlation of fatigue with tness
measures. Neither fatigue nor tness was signicantly correlated with disease activity, disease damage, or QOL measures.
Conclusion. Young SLE patients have lower aerobic tness than reference norms. The 6MW may be used as a marker of
tness, but it is preferable to determine VO2 with a graded exercise test. Fatigue is a signicant symptom in young SLE
patients. The application of fatigue measures in young persons is exploratory. The relationship between fatigue and
aerobic tness is not clear.

INTRODUCTION
The onset of systemic lupus erythematous (SLE) occurs in
childhood or adolescence for 15% of affected individuals. Young persons with SLE generally have severe disease
at onset, requiring high-dose corticosteroid and immunosuppressive drugs for disease control (1 4). A majority
have organ system disease (kidney, lung, central nervous
system, heart) either at diagnosis or early in the course of
their disease (1). The combination of active disease and
side effects of corticosteroid treatment, such as weight
gain, results in difculties in normal functioning for children with SLE. Many children with SLE discontinue their
Supported by a grant from the British Columbia Childrens Hospital Telethon.
1
Kristin M. Houghton, MD, FRCPC, FAAP, Lori B. Tucker,
MD, FAAP, James E. Potts, PhD: British Columbia Childrens
Hospital, Vancouver, British Columbia, Canada; 2Donald C.
McKenzie, MD, PhD: Human Kinetics and University of
British Columbia, Vancouver, British Columbia, Canada.
Address correspondence to Kristin M. Houghton, MD,
FRCPC, FAAP, K4-123 ABC, 4480 Oak Street, Vancouver,
British Columbia, Canada V6H 3V4. E-mail: khoughton@
cw.bc.ca.
Submitted for publication June 14, 2007; accepted in revised form October 12, 2007.

participation in sports or physical activity at the time of

diagnosis (4).
Fatigue is one of the most prevalent clinical manifestations of SLE. Fatigue is a nonspecic and highly subjective
symptom, and perceived severity may be related to psychosocial and disease- and treatment-related factors (5).
Fatigue can be profound and often affects an individuals
ability to function. Several studies have suggested a correlation of fatigue with disease activity, pain, mood, and
sleep dysregulation (2,3,5 8). A positive correlation between fatigue and bromyalgia (FM) associated with SLE
has been demonstrated in adults (9). Physical inactivity
and deconditioning may also play a role in fatigue and
quality of life (QOL) in patients with SLE.
Despite the important role of fatigue in adults with SLE,
there have been no studies reporting the incidence of
fatigue in children with SLE and its impact on their daily
lives. In addition, the extent of physical deconditioning
and inactivity among children with SLE has not been
studied. Aerobic tness diminishes after adolescence and
has a strong positive relationship with general health. Recent large cohort studies have conrmed the importance of
exercise capacity in predicting mortality among both men
and women (10,11). The role of exercise in children with
chronic disease is an area in need of clarication.
537

538
The purpose of the present study was to measure tness,
fatigue, and QOL in a cohort of young patients with SLE.
Our hypothesis was that young patients with SLE would
have reduced aerobic tness compared with reference
norms and that fatigue would be inversely related to aerobic capacity. The secondary objectives of this study were
to test the use of a modied Kids Fatigue Severity Scale
(K-FSS), to examine the relationship between maximal
and submaximal exercise tests in our study population,
and to determine an equation for predicting maximum
oxygen consumption (VO2peak) and ventilatory anaerobic
threshold (VAT) from the distance walked in 6 minutes
(6MW) (12).

PATIENTS AND METHODS

Participants. Patients ages 1220 with a denite diagnosis of SLE who were followed at the Pediatric Rheumatology Program at British Columbia Childrens Hospital
were invited to participate (13,14). Patients were excluded
if they had been diagnosed within the preceding 3 months,
were 18 years of age at diagnosis, or had active organ
system disease or treatment morbidity (including renal
insufciency, pericarditis, pleuritis, serositis, myositis,
avascular necrosis) precluding participation in exercise
tests. Study assessments occurred between January 2006
and March 2007. All patients and caregivers provided
assent and consent prior to participation. Ethical approval
was obtained from the University of British Columbias
Clinical Research Ethics Board and the hospitals Research
Review Committee.
Methods. Study participants underwent a clinical assessment by a rheumatologist (KMH) the same day as the
exercise testing. Assessment included a complete physical
examination (including tender point count) and data collection for age, sex, disease duration, history of previous
cardiac or respiratory disease (echocardiogram, electrocardiogram [EKG], and pulmonary function test results), and
current medications.
Anthropometric measures. Height (Harpenden Stadiometer, London, England) and body mass (SECA electronics, Hamburg, Germany) were measured to the nearest 0.1
cm and 0.1 kg, respectively. Body mass index (BMI) was
calculated (kg/m2). Body composition (percent body fat)
was estimated from the sum of skinfold measurements of
the subscapular and triceps region (Baseline Skinfold Caliper, AMG Medical, Montreal, Quebec, Canada) according
to the equation developed by Slaughter et al (15). Obesity
was dened as a BMI or triceps skinfold greater than the
95th percentile according to reference data (16).
Fitness measures. Aerobic tness. Maximal aerobic capacity (VO2peak) is the level of oxygen uptake that cannot
be surpassed with increased exercise intensity. VO2peak
was measured by a graded treadmill exercise test to volitional fatigue. Treadmill speed was kept constant at 5
km/hour and the grade was increased 2.5% every 2 min-

Houghton et al
utes. Open-circuit spirometry was used to determine respiratory exchange variables during exercise and was averaged over 15-second intervals. Patients breathed through
a Hans Rudolph valve (Hans Rudolph, Kansas City, MO).
Using a MOXUS Metabolic Cart (AEI Technologies, Pittsburgh, PA), expired gases were analyzed by O2 and CO2
analyzers (models S-3A and CD-3A, respectively; AEI
Technologies). The system was calibrated before each test
with standard gases of known O2 (20.93% and 15.00%)
and CO2 (0.03% and 5.02%) concentrations. Volume was
calibrated and veried using a 3-liter syringe (Hans Rudolph). Measurements included total test duration,
VO2peak (dened as the highest VO2 achieved in any 15second period), maximal ventilation, peak respiratory exchange ratio (RER), maximal heart rate (MHR), and percent
age-predicted MHR. Blood pressure in the right arm was
measured manually at baseline, every 5 minutes during
exercise, and 5 minutes postexercise with a sphygmomanometer. A maximal effort was dened as achieving an
RER 1.0, or reaching an MHR 195 (17). VO2peak was
compared with American population data (18).
Submaximal exercise intensity was determined by the
VAT. VAT, dened as the point at which oxygen supply
no longer meets oxygen demands of exercising muscle, is
a surrogate measure of lactate threshold (19). We used the
point of inection of the maximal ventilation/VO2, with
the maximal ventilation/CO2 production constant or declining as the VAT (20).
Submaximal aerobic capacity is exercise performed below the maximal oxygen uptake. Submaximal tests are
often used to predict VO2peak. Submaximal aerobic capacity was determined from the 6MW. The walk test was
performed in our clinic (50-meter measured loop) with
standard encouragement (21). Distance walked in meters,
MHR, average HR, and rating of perceived exertion (RPE)
were recorded. RPE was recorded as a number value from
1 to 10 per the Childrens Effort Rating Scale (22). Reference values for the 6MW were obtained from healthy
white and Chinese populations (23,24). Children of other
Southeast Asian background or American Indians were
compared with the reference Chinese data, which are
slightly lower than the reference data for whites.
Strength. Isometric quadriceps strength of the dominant
leg and grip strength were measured with a CITEC handheld dynamometer (CT 3001; C.I.T. Technics, Groningen,
The Netherlands); the best effort of 3 trials was recorded
(rectus femoris was measured with the hip and knee exed
at 90 and the ankle supported by the examiner with the
dynamometer on the anterior surface of the distal thigh).
Results were compared with reference population data
(25).
Flexibility. Flexibility of the dominant hamstrings and
gastrocnemius muscle groups was measured with a goniometer (Incstar Corporation, Stillwater, MN). Popliteal angles and ankle dorsiexion were recorded to the nearest
degree.
Patient questionnaires. The K-FSS was used to assess
fatigue. The FSS is a validated questionnaire developed for
adults that measures the impact of fatigue on activities of

Fitness in Pediatric Lupus

539

Table 1. Kids Fatigue Severity Scale and Fatigue Severity Scale (12)*
Question
1
2
3
4
5
6
7
8
9

Modied kids statement

Adult statement

I dont feel like doing anything when I am

fatigued.
Exercise brings on my fatigue.
I am easily fatigued.
Fatigue interferes with things like walking,
running, or climbing stairs for me.
Fatigue causes frequent problems for me.
My fatigue makes it hard to do physical
activities for very long.
Fatigue interferes with things I need to do,
like going to school.
Fatigue is among my 3 biggest problems.
Fatigue interferes with my social life
(spending time with friends).

My motivation is lower when I am fatigued.

Exercise brings on my fatigue.
I am easily fatigued.
Fatigue interferes with my physical
functioning.
Fatigue causes frequent problems for me.
My fatigue prevents sustained physical
functioning.
Fatigue interferes with carrying out certain
duties and responsibilities.
Fatigue is among my 3 biggest problems.
Fatigue interferes with my work, family, or
social life.

* Patients choose a number from 1 to 7 corresponding to their level of agreement with each statement (1 strongly disagree and 7 strongly agree).

daily living (12). The questions on the FSS were modied

so that they were appropriate for childrens language and
activities (Table 1). Scores range from 1 to 7 with higher
scores indicative of more fatigue. Fatigue was dened as
present if the K-FSS score was 3.0 (5).
Habitual physical activity levels were assessed using the
Habitual Activity Estimation Scale (HAES). The HAES has
been validated in healthy children and children with
chronic disease. The Two Days of My Life questionnaire
asks children to recall typical weekday and weekend daily
activity, estimating the time spent inactive (e.g., sleeping),
somewhat inactive (e.g., sitting), somewhat active (e.g.,
walking), and active (e.g., running) (26). Patients with
summary scores reecting 3 hours per week of activity
were considered active (27).
QOL was measured with the Child Health Questionnaire
(CHQ), a generic validated questionnaire measuring the
QOL of children ages 517 years. The CHQ child version is
a prole measure with 78 questions that measures physical
functioning, social and emotional functioning, mental
health and behavior, self-esteem, and family functioning.
Reference norms are available, with higher scores indicative of higher QOL (28).
Disease measures. The Systemic Lupus Erythematosus
Disease Activity Index (SLEDAI) was used to assess disease activity (29). The SLEDAI assesses 24 clinical and
laboratory measures of SLE activity with a score range of
0 105; a higher score corresponds to higher disease activity. The following activity categories have been dened on
the basis of SLEDAI scores: no activity (SLEDAI 0), mild
activity (SLEDAI 15), moderate activity (SLEDAI
6 10), high activity (SLEDAI 1119), and very high
activity (SLEDAI 20) (30). The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (SDI) was used to assess disease damage (31). Items include disease- and treatmentrelated morbidities. Scores range from 0 to 47 and items
must be present continuously for 6 months to be scored
as damage.

Statistical analysis. Descriptive statistics were calculated for tness measures, fatigue, and QOL. Mean SD
values and Z scores are presented. The association between continuous variables was assessed using Pearsons
and Spearmans correlation coefcients. Linear regression
models were used to explore the relationships between
aerobic capacity and fatigue, QOL, disease activity, and
disease damage. Correlation coefcients of 0.3 0.5, 0.5
0.7, and 0.71.0 indicated low, moderate, and high correlations, respectively. The 6MW distance, walking MHR,
BMI, and SLEDAI scores were correlated with VO2peak and
with VAT to determine which variables to enter into a
stepwise regression equation to predict VO2 and VAT. The
signicance level for all tests was set at P values less than
0.05, except for determining which variables to enter into
stepwise regression, which was set P values less than 0.10.
Fishers exact test was used for a 2 2 contingency table.
Statistics were performed using SPSS 15.0 (SPSS, Chicago,
IL).

RESULTS
At the time of the study, 32 of the 48 patients with SLE
who were followed in our clinic were eligible to participate. Of these, 15 participated. The majority of patients
who declined cited lack of time as the reason. Sixteen
patients with SLE were excluded (9 patients had active
disease precluding exercise testing, 2 patients were diagnosed within 3 months of the study closing, and 5 were
deemed ineligible because they were 12 years of age).
Demographic, clinical, and disease factors are shown in
Table 2. The mean SD age was 16.5 1.9 years. The
mean disease duration was 45 33 months. All patients
were taking hydroxychloroquine, 10 (67%) were taking
prednisone, and 10 (67%) were taking at least 1 noncorticosteroid immunosuppressant. Disease activity and disease damage were variable (Table 2).
Only 1 patient met our operational denition of obesity.
Several patients had a few tender points, but none met the
ACR criteria for FM (32,33). The clinical cardiorespiratory

540

Houghton et al

Table 2. Patient demographic, clinical, and disease measures*

Patient

Age, years

Sex

Ethnicity

Disease duration, months

Medications

SLEDAI

SDI

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Mean SD
Median (range)

16.7
18.5
14.8
14.4
17.0
17.8
16.6
17.6
16.8
14.8
19.6
18.6
14.0
12.8
17.1
16.5 1.9

F
F
F
F
F
F
M
M
F
F
F
F
M
F
F

East Indian
Filipino
Sri Lankan
Chinese
Chinese
American Indian
Vietnamese
White
Chinese
White
Chinese
White
Vietnamese
White
Vietnamese

6
6
43
22
59
132
32
41
57
4
68
56
49
25
71
45 33

1, 2, 5, 10
1, 2, 5, 8, 9
2, 4
1, 2, 6, 9
2, 6, 7
1, 2, 5, 9
1, 2, 4, 11, 12
2, 7, 13
1, 2
1, 2, 13
2
1, 2, 4
1, 2, 5, 79, 11
1, 2, 4
2

4
12
2
6
0
12
4
0
2
2
0
5
16
16
2

2
2
0
0
0
1
0
0
0
0
0
2
1
0
0

4 (016)

0 (02)

* SLEDAI Systemic Lupus Erythematosus Disease Activity Index; SDI Systemic Lupus International Collaborating Clinics/American College of
Rheumatology Damage Index.
1 prednisone; 1 10 gm/day; 2 hydroxychloroquine; 3 methotrexate; 4 azathioprine; 5 cyclophosphamide; 6 mycophenolate
mofetil; 7 aspirin; 8 hydrochlorothiazide; 9 enalapril; 10 intravenous immunoglobulin; 11 amlodipine; 12 losartan potassium; 13
naproxen.

examination, EKG, and echocardiogram were normal in all

patients. There were mild diffusion abnormalities on pulmonary function tests in 5 (33%) patients, but all had
normal oxygen saturation. One patient had mild restrictive
lung disease.
Fitness. Fitness measures are shown in Tables 3 and 4.
There was a large range in tness measures, with a mean
SD VO2 peak of 31.1 7.9 ml/minute/kg corresponding to a
mean SD Z score of 1.75 1.16. Five (33%) patients
had Z scores of 2 or lower. Only 2 (13%) patients had a
VO2 peak greater than 1 Z score of reference norms (18).

Distance covered during the 6MW was lower than age-,

sex-, and ethnicity-matched normative data for white and
Chinese children (34,35). The mean SD distance covered
was 548 110 meters, corresponding to a mean Z score of
2.4 2.3. Nine (60%) patients had Z scores of 2 or
lower.
The mean SD VAT was 20.1 1.3 ml/minute/kg for
boys compared with a normative mean value of 22 5.0
ml/minute/kg (P 0.51). The mean SD VAT was 17.0
5.8 ml/minute/kg for girls compared with a normative
mean value of 20.0 4.0 ml/minute/kg (P 0.03) (18).
VAT usually corresponds to 60 70% of VO2peak (36 38).

Table 3. Fitness measures*

Patient
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Mean
SD

BMI,
kg/m2

% body
fat

VO2 test
duration,
minutes

VO2peak,
% age/
VO2peak,
sex
ml/kg/ predicted
mind
(18)

VO2peak
Z score

RER

VO2
MHR

%
VAT
VAT, ml/ (VAT/
kg/min
VO2)

6MW,
meters

6MW
Z score

6MW
MHR

20.0
28.1
8.75
17.5
44
3.70
1.12
178
11.9
66
470
4.3
156
23.2
25.1
25.1
20.5
51
3.21
0.82
200
9.1
54
575
1.6
158
17.5
21.2
21.2
28.4
66
2.34
0.75
152
ND
ND
595
1.1
141
22.3
25.4
25.4
33.3
78
1.55
0.96
203
13.9
36
512
3.2
126
19.8
18.1
18.1
29.8
74
1.69
0.84
196
15.0
48
430
5.4
124
35.6
51.7
51.7
21.9
55
2.98
0.74
180
14.6
67
480
4.1
128
20.1
23.0
23.0
34.7
68
1.71
1.00
171
20.7
54
505
2.8
134
21.4
21.3
21.3
38.9
76
1.27
1.16
181
22.4
53
370
5.8
125
18.0
30.4
30.4
32.2
80
1.29
1.10
181
19.7
45
600
1.0
116
22.1
25.7
25.7
38.2
89
0.76
1.14
206
27.5
55
630
0.65
128
19.7
25.4
25.4
30.9
77
1.51
1.28
193
20.4
57
450
4.8
136
20.3
26.7
26.7
24.1
60
2.62
1.17
160
ND
ND
550
2.3
134
20.2
18.9
18.9
35.1
66
1.64
1.09
167
19.4
60
680
0.17
132
16.9
23.3
23.3
48.2
119
1.17
0.99
195
41.1
66
814
3.0
141
24.2
30.4
30.4
33.2
83
1.13
1.04
197
17.7
52
560
2.0
139
21.4 4.4 26.3 7.9 14.7 4.6 31.1 7.9 72 18 1.75 1.16 1.01 0.16 184 16 17.4 5.6 55 9 548 110 2.4 2.3 135 11

* BMI body mass index; VO2 oxygen consumption; VO2peak maximum oxygen consumption; RER respiratory exchange ratio; MHR maximal
heart rate; VAT ventilatory anaerobic threshold; 6MW distance walked in 6 minutes; ND not determined.

Fitness in Pediatric Lupus

541

* Values are the mean SD. VO2peak maximum oxygen

consumption.

stage renal disease population; the SD is only available for

individual items, not subscales or general scores. The CHQ
general health perceptions (CHQ-GH) and self-esteem
were lower in our patients with SLE than reference norms.
There were no signicant differences between our patients
as a group and the reference sample on measures of physical functioning, social and emotional functioning, mental
health and behavior, or pain and pain behaviors. Our
patients had more disruption of family functioning, with
lower scores for family activities but not family cohesion.

Our patients mean percent VAT was 55% 9%. The VAT
could not be determined in 2 patients.
Compared with age-matched norms, rectus femoris
strength was low, with a mean SD of 185 70N corresponding to a mean Z score of 2.5 1.9 (25). Eight (53%)
patients had Z scores of 2 or lower. The mean grip
strength was 107 22N. Normative data are available for
3-point grip but not grip strength. Flexibility of the hamstrings was suboptimal in all patients, with none having
popliteal angles 160 (mean SD 139 7). Achilles
exibility was representative of the adolescent population
(mean SD 10 4).
Results from patient self-report of fatigue, habitual activity levels, and QOL measures are shown in Table 5. The
mean SD K-FSS score was 3.8 1.2. Ten (67%) patients
reported a K-FSS score 3.0, indicating signicant fatigue
(5). Using the HAES, 8 (53%) children reported a physically active lifestyle. Fatigue and activity level were not
related (P 0.38). For the CHQ, normative means are
available for a reference school-based population and end-

Correlations. VAT showed a moderate positive correlation with 6MW distance (R 0.61, P 0.026), whereas
VO2peak and 6MW distance were positively correlated, but
the correlation was not statistically signicant (R 0.45,
P 0.09). The 6MW distance and MHR were independent
variables in stepwise regression to predict VO2peak. BMI
and SLEDAI scores were not signicantly correlated with
VO2peak and were not entered into the regression equation
(Table 6). The regression equation for predicting VO2peak
(pVO2peak) from distance walked and MHR in the 6MW
was as follows: pVO2peak (ml/minute/kg) 57.1 [0.038
distance (meters)] (0.35 MHR) (R 0.67, P 0.027,
standard error of the estimate [SEE] 6.1) (Figure 1A). The
regression equation for predicting VAT (pVAT) was as
follows: pVAT (ml/minute/kg) 1.44 0.029 [distance
(meters)] (R 0.61, P 0.1, SEE 4.6) (Figure 1B).
There was no signicant correlation of fatigue with
VO2peak and VAT (R 0.01 and 0.10, respectively). The
presence/absence of fatigue and normal/subnormal VAT
was not correlated (P 0.65 by Fishers exact test). There

Table 4. VO2peak norms (18)*

VO2peak
Age, years
12, 13
14, 15
18

Girls

Boys

40.5 6.6
42.9 6.2
40.1 6.1

49.4 8.8
53.3 11.1
51.0 9.5

Table 5. Patient questionnaires: fatigue, habitual activity levels, and quality of life measures*

Present study
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 8
Patient 9
Patient 10
Patient 11
Patient 12
Patient 13
Patient 14
Patient 15
Mean SD
Reference
SLE adults, mean SD
Healthy adults, mean SD
Reference norms
End-stage renal disease

K-FSS

HAES

CHQ-PF

CHQ-GH

CHQ-SE

CHQ-FA

CHQ-FC

4.4
4.4
2.8
3.8
3.8
3.3
4.8
2.7
2.9
6.0
4.2
5.6
2.8
4.4
1.3
3.8 1.2

Active
Nonactive
Nonactive
Nonactive
Nonactive
Active
Active
Active
Nonactive
Active
Nonactive
Nonactive
Active
Active
Active
53% active

48
81
89
89
92
89
89
64
96
66
96
66
100
100
96
84 16

59
45
43
79
60
32
57
52
65
34
59
52
66
43
66
54 13

87
58
94
94
64
66
69
80
75
51
62
66
96
46
89
73 16

87
58
94
94
64
66
69
80
75
51
62
66
96
46
89
54 21

85
30
85
85
60
30
60
85
85
60
60
60
85
30
30
62 23

88
73

65
49

82
68

62
NA

6085
NA

4.6 1.5
2.3 1.7

* K-FSS Kids Fatigue Severity Scale; HAES Habitual Activity Estimation Scale; CHQ Child Health Questionnaire; PF physical function; GH
general health; SE self-esteem; FA family activities; FC family cohesion; SLE systemic lupus erythematosus; NA not available.
Fatigue was dened as present if K-FSS score was 3.0.
Active was dened as 3 hours/week.

542

Houghton et al

Table 6. Correlations of variables considered for

regression equation for pVO2peak*
6MW distance,
meters
6MW MHR
R
P
BMI
R
P
SLEDAI
R
P
VO2peak
R
P

6MW
MHR

BMI

SLEDAI

0.157
0.575
0.305
0.268

0.039
0.894

0.622
0.013

0.313
0.275

0.207
0.459

0.450
0.09

0.419
0.10

0.385
0.157

and CHQ-GH (R 0.63, P 0.02). There was a moderate

negative correlation between disease damage (SDI) and
QOL measures for CHQ-PF (R 0.51, P 0.05) but not
CHQ-GH (R 0.153, P 0.59). There was a trend toward
a low negative correlation between disease activity (SLEDAI) and CHQ-PF, but not CHQ-GH (CHQ-PF: R 0.30,
P 0.28; CHQ-GH: R 0.21, P 0.46).

DISCUSSION

0.073
0.80

* pVO2peak predicted maximum oxygen consumption; SLEDAI

Systemic Lupus Erythematosus Disease Activity Index; see Table 3
for additional denitions.
Variables entered into regression equation.

was no signicant correlation between fatigue and SLEDAI

scores, SDI scores, or QOL measures.
There was no signicant correlation between VAT and
CHQ physical function (CHQ-PF; R 0.19, P 0.53), but
there was a moderate negative correlation between VAT

Figure 1. A, Correlation of actual maximum oxygen consumption

(VO2peak [ml/minute/kg]) versus predicted VO2peak values. B, Correlation of actual ventilatory anaerobic threshold (VAT [ml/kg/
minute]) values versus predicted VAT values. pVO2peak predicted VO2peak; 6MW distance walked in 6 minutes; MHR
maximal heart rate; pVAT predicted VAT.

To our knowledge, our study is the rst to report on tness

and fatigue in pediatric SLE. We found that young patients
with SLE have reduced aerobic tness compared with ageand sex-matched reference norms, but tness was variable,
with some subjects achieving predicted performance. The
average VO2peak was 31 ml/minute/kg, which corresponds
to moderate impairment in an adolescent population (18).
Studies in adults with SLE have demonstrated reduced
tness with lower levels of aerobic capacity and muscle
strength, greater fatigue, and greater disability than
healthy sedentary controls (2). Reduced aerobic capacity
in patients with SLE is largely thought to be due to deconditioning of the peripheral muscles and suboptimal oxygen utilization. Primary lung disease is not thought to be a
major contributor to decreased exercise capacity in most
patients with SLE, and based on the minor pulmonary
function test abnormalities seen in our patients, it is unlikely that pulmonary disease was a signicant contributor
to their poor aerobic capacity. Coronary artery disease is
recognized as a signicant cause of morbidity and mortality in patients with SLE and its effect on the pediatric
population is not clear (39). A study of 40 pediatric patients with SLE found that 16% had qualitative abnormalities of myocardial perfusion but normal left ventricular
function at rest and during exercise (40). Cardiac investigations were normal in all of our patients.
The distance covered in the 6MW was lower than reported age-, sex-, and ethnicity-matched reference norms,
with a mean Z score of 2.4. Submaximal exercise tests
may be better suited to individuals, like adolescents with
SLE, whose maximal effort is limited by pain or fatigue
rather than exertion. The 6MW has been proposed as the
best indicator of functional capacity among all submaximal exercise tests (41). Most activities of daily living are
performed at submaximal levels of exertion, and submaximal tests may better represent physical capacity. The validity of the 6MW in predicting VO2peak is unclear, with
some studies reporting a high correlation and others reporting no signicant correlation (23,24,35,42). A study of
30 women with rheumatic disease (5 with SLE) found
submaximal exercise testing using a single-stage, self-selected treadmill walking speed to be a reliable and valid
measure of aerobic capacity (43). A recent study of healthy
Chinese children found that the 6WM was signicantly
correlated with VO2peak (R 0.44, P 0.0001) (35). Our
patients achieved 60 80% MHR (mean 68%), and
pVO2peak from the 6MW distance and MHR was moderate
(R 0.67, P 0.027), but the correlation was not signicant, likely due to our small sample size. The observed low
negative correlation between pVO2peak and MHR during

Fitness in Pediatric Lupus

submaximal exercise is consistent with physiologic
changes associated with tness training. A reduction of
resting and submaximal HR is a sensitive response to
training, and conversely an increase in resting and submaximal HR is seen with detraining and deconditioning.
The most common measure of submaximal exercise intensity is VAT. VAT may be related to fatigue and function
(19). VAT usually corresponds to 60 70% of VO2peak and
is higher in trained individuals (36 38,44). One study
found a mean SD VAT of 60% 9% with slightly lower
ratios in older children (44). Exercise above the VAT leads
to increased anaerobic metabolism with lactate accumulation and secretion of stress hormones. Patients can usually
exercise and perform activities of daily living safely below
their VAT. A study of 21 women with SLE without cardiopulmonary complications found low aerobic capacity
and low VAT, suggesting that a low VAT may contribute to
fatigue (45). In a study of women with FM, impaired VAT
and VO2peak were found; the majority of patients were not
able to achieve maximum effort (46).
As a group, our female patients had a lower VAT than
reference norms. The VAT could not be determined in 2
patients because of erratic breathing patterns; this problem
has been reported by other researchers (19,47). A lower
VAT may be related to early fatigue, because some activities of daily living may be above an individuals VAT,
leading to an inability to sustain that level of activity.
However, we did not nd a correlation between presence/
absence of fatigue and normal/subnormal VAT in our patients. In clinical practice, exercise prescription using the
HR at VAT as a target HR may help guide conditioning and
training programs. Improvements in VAT are seen before
VO2peak during aerobic training, and serial exercise testing
may allow monitoring of physical tness.
We used measures of isometric strength for ease of testing and reproducibility in the clinic. However, isometric
strength testing does not give any information on muscular
endurance and, therefore, does not necessarily correlate
with aerobic tness. Anaerobic tness depends predominantly on nonoxidative energy turnover and is related to
local characteristics of working muscle groups. Eight
(53%) patients demonstrated decreased rectus femoris
strength with Z scores of 2 or lower (25). Anaerobic
tness was not tested in this study, but in future studies it
will be interesting to examine because there is indication
of a positive relationship between functional ability and
anaerobic tness in other pediatric chronic rheumatic disease populations (48).
The K-FSS was used as a measure of fatigue; this is a
new measure based on the FSS, which was modied by
our group for use in pediatric populations. The FSS is a
well-validated questionnaire developed for adults that
measures the impact of fatigue on activities of daily living
(12). This instrument has been used in a number of studies
of fatigue in adult patients with SLE, and has been shown
to be stable over time, sensitive to clinical change, and able
to discriminate between fatigue and depressive symptoms
(5,12). Comparisons have not previously been made between pediatric and adult patients with SLE. Mean SD
FSS scores are reported as 4.6 1.5 and 2.3 1.7 for
adults with SLE and healthy adults, respectively. Our av-

543
erage score of 3.8 was lower than that for adults with SLE
but higher than that for healthy adults. Ten of our patients
(67%) reported fatigue as a signicant problem. Reference
values for healthy children are not currently available for
comparison. The reported fatigue had no signicant correlation with aerobic tness or QOL measures.
QOL was measured with the CHQ. Our patients had
lower general health perceptions and self-esteem than a
reference school population, but scored higher than an
end-stage renal disease population (28). Our patients had
more disruption of family functioning, with lower scores
for family activities, but not family cohesion. Reference
values for family functioning are not available for other
chronic diseases, but it is intuitive that caring for a child
with chronic illness may disrupt some family activities
and scheduling. There were no signicant differences between our patients as a group and a reference sample on
measures of physical functioning, social and emotional
functioning, mental health and behavior, and pain and
pain behaviors. There was a moderate negative correlation
between measures of physical function and disease damage. There was no signicant correlation between disease
activity and QOL or fatigue. The SLEDAI does not include
subjective symptoms such as fatigue, and this may partially explain the low correlation with patient disease activity, QOL, or fatigue. Use of the SLAM (Systemic Lupus
Activity Measure) in future studies should be considered
because scoring relies on the reporting of symptoms by the
patient rather than objective documentation as required by
the SLEDAI (49).
This study has several limitations. Small numbers of
patients, enrollment bias, and absence of controls limit
generalization of our results. Procedural limitations include measures of fatigue and the exercise protocol. The
K-FSS does not have normative data for young persons and
its use is exploratory. The same exercise protocol was used
for all patients to standardize testing, but individual protocols may have allowed for maximal tests in all patients.
Two patients (patients 3 and 6) did not achieve a maximal
effort. Not achieving a maximal effort may be due to a
submaximal test or termination of the test prior to exhausting cardiopulmonary reserve, possibly due to mental or
muscular fatigue. The exercise test is a maximal test to
volitional fatigue and should ideally last 8 12 minutes.
The standardized protocol was based on studies conducted in adults with SLE but underestimated our patients tness, with exercise lasting 15 minutes in 8
(53%) patients, thus becoming more of an endurance test
than a maximal test (17). Normative VO2peak data are for
white children using the Bruce protocol (both speed and
slope increase from one stage to the next) (18). Ethnic
differences may exist and our protocol used a modied
Balke protocol (xed speed with slope increase from one
stage to the next) (17).
Few randomized control studies have looked at exercise
intervention in the adult SLE population and all have
demonstrated either no effect or a positive effect on fatigue
and exercise capacity, with no worsening of disease activity. Supervised cardiovascular training programs report
signicant improvements in tness, whereas unsupervised
home-based interventions report improved measures of

544

Houghton et al

fatigue or QOL without signicant improvements in aerobic tness (50 55). Exercise intervention studies involving
the pediatric SLE population have not been published.
In summary, children and young persons with SLE have
lower aerobic tness than reference norms. The 6MW may
be used as a marker of aerobic tness but it is preferable to
determine VO2peak with a graded exercise test. This study
conrms that fatigue is a signicant symptom in young
patients with SLE. The application of fatigue measures in
young persons is exploratory. The relationship between
fatigue and aerobic tness and QOL is not clear. Future
studies are needed to determine the validity and utility of
fatigue measures in young patients and to research the
effects of exercise therapy on tness, VAT, fatigue, and
QOL. Exercise capacity is increasingly recognized as an
important predictor of mortality (10,11). Fitness as measured by VO2peak may emerge as an important outcome
measure for children and young persons with SLE.

11.
12.

13.

14.

15.

16.

ACKNOWLEDGMENTS
Thanks to Natalie Taha, BSc, HKinetics, and Astird DeSouza, MSc, HKinetics, for their help with exercise testing.

17.
18.

AUTHOR CONTRIBUTIONS
Dr. Houghton had full access to all of the data in the study and
takes responsibility for the integrity of the data.
Study design. Houghton, Tucker, McKenzie, Potts.
Acquisition of data. Houghton, Potts.
Analysis and interpretation of data. Houghton, Tucker, McKenzie, Potts.
Manuscript preparation. Houghton, Tucker, McKenzie, Potts.

REFERENCES
1. Tucker LB, Menon S, Schaller JG, Isenberg DA. Adult- and
childhood-onset systemic lupus erythematosus: a comparison
of onset, clinical features, serology, and outcome. Br J Rheumatol 1995;34:866 72.
2. Tench C, Bentley D, Vleck V, McCurdie I, White P, DCruz D.
Aerobic tness, fatigue, and physical disability in systemic
lupus erythematosus. J Rheumatol 2002;29:474 81.
3. Wysenbeek AJ, Leibovici L, Weinberger A, Guedj D. Fatigue in
systemic lupus erythematosus: prevalence and relation to disease expression. Br J Rheumatol 1993;32:6335.
4. Petty RE, Laxer RM. Systemic lupus erythematosus. In:
Cassidy JT, Petty RE, Laxer R, Lindsley C, editors. Textbook of
pediatric rheumatology. 5th ed. Philadelphia: Elsevier; 2005.
p. 34291.
5. Krupp LB, LaRocca NG, Muir J, Steinberg AD. A study of
fatigue in systemic lupus erythematosus. J Rheumatol 1990;
17:1450 2.
6. Zonana-Nacach A, Roseman JM, McGwin G Jr, Friedman AW,
Baethge BA, Reveille JD, et al, and the LUMINA Study Group.
Systemic lupus erythematosus in three ethnic groups. VI.
Factors associated with fatigue within 5 years of criteria diagnosis. Lupus 2000;9:1019.
7. McKinley PS, Ouellette SC, Winkel GH. The contributions of
disease activity, sleep patterns, and depression to fatigue in
systemic lupus erythematosus: a proposed model. Arthritis
Rheum 1995;38:826 34.
8. Tench CM, McCurdie I, White PD, DCruz DP. The prevalence
and associations of fatigue in systemic lupus erythematosus.
Rheumatology (Oxford) 2000;39:1249 54.
9. Wang B, Gladman DD, Urowitz MB. Fatigue in lupus is not
correlated with disease activity. J Rheumatol 1998;25:8925.
10. Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood

19.
20.
21.

22.
23.

24.
25.

26.

27.
28.
29.

30.

31.

JE. Exercise capacity and mortality among men referred for

exercise testing. N Engl J Med 2002;346:793 801.
Gulati M, Black HR, Shaw LJ, Arnsdorf MF, Merz CN, Lauer
MS, et al. The prognostic value of a nomogram for exercise
capacity in women. N Engl J Med 2005;353:468 75.
Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale: application to patients with multiple
sclerosis and systemic lupus erythematosus. Arch Neurol
1989;46:11213.
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rotheld
NF, et al. The 1982 revised criteria for the classication of
systemic lupus erythematosus. Arthritis Rheum 1982;25:
12717.
Hochberg MC, for the Diagnostic and Therapeutic Criteria
Committee of the American College of Rheumatology. Updating the American College of Rheumatology revised criteria for
the classication of systemic lupus erythematosus [letter].
Arthritis Rheum 1997;40:1725.
Slaughter MH, Lohman TG, Boileau RA, Horswill CA, Stillman RJ, Van Loan MD, et al. Skinfold equations for estimation
of body fatness in children and youth. Hum Biol 1988;60:
709 23.
Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a
standard denition for child overweight and obesity
worldwide: international survey. BMJ 2000;320:1240 3.
Bar-Or O, Rowland TW. Procedures for exercise testing in
children. In: Pediatric exercise medicine. Champaign (IL):
Human Kinetics; 2004. p. 343 67.
Ahmad F, Kavey RE, Kveselis DA, Gaum WE, Smith FC.
Responses of non-obese white children to treadmill exercise.
J Pediatr 2001;139:284 90.
Wasserman K, Whipp BJ, Koyl SN, Beaver WL. Anaerobic
threshold and respiratory gas exchange during exercise.
J Appl Physiol 1973;35:236 43.
Beaver WL, Wasserman K, Whipp BJ. A new method for
detecting anaerobic threshold by gas exchange. J Appl Physiol
1986;60:2020 7.
ATS Committee on Prociency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the
six-minute walk test. Am J Respir Crit Care Med 2002;166:
1117.
Eston RG, Lamb KL, Bain A, Williams AM, Williams JG.
Validity of a perceived exertion scale for children: a pilot
study. Percept Mot Skills 1994;78:6917.
Guyatt GH, Sullivan MJ, Thompson PJ, Fallen EL, Pugsley SO,
Taylor DW, et al. The 6-minute walk: a new measure of
exercise capacity in patients with chronic heart failure. Can
Med Assoc J 1985;132:919 23.
Nixon PA, Joswiak ML, Fricker FJ. A six-minute walk test for
assessing exercise tolerance in severely ill children. J Pediatr
1996;129:362 6.
Beenakker EA, van der Hoeven JH, Fock JM, Maurits NM.
Reference values of maximum isometric muscle force obtained in 270 children aged 4-16 years by hand-held dynamometry. Neuromuscul Disord 2001;11:441 6.
Hay JA. Development and testing of the Habitual Activity
Estimation scale. In: Armstrong N, Weisman J, Kirby B, editors. Children and exercise XIX: promoting health and wellbeing. XIXth International Symposium of Pediatric Work
Physiology. Exeter (WA): Singer; 1997. p. 1259.
Healthy Active Living Committee. Healthy active living for
children and youth. Paediatr Child Health 2002;7:339 45.
Landgraf JL, Abetz L, Ware JE. The CHQ users manual. 1st ed.
Boston: The Health Institute, New England Medical Center;
1996.
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang
CH, and the Committee on Prognosis Studies in SLE. Derivation of the SLEDAI: a disease activity index for lupus patients.
Arthritis Rheum 1992;35:630 40.
Cook RJ, Gladman DD, Pericak D, Urowitz MB. Prediction of
short term mortality in systemic lupus erythematosus with
time dependent measures of disease activity. J Rheumatol
2000;27:18925.
Gladman DD, Urowitz MB, Goldsmith CH, Fortin P, Ginzler E,

Fitness in Pediatric Lupus

32.
33.

34.
35.
36.

37.
38.

39.
40.

41.

42.
43.

Gordon C, et al. The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus. Arthritis Rheum 1997;40:809 13.
Wolfe F. Fibromyalgia. Rheum Dis Clin North Am 1990;16:
68198.
Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C,
Goldenberg D, et al. The American College of Rheumatology
1990 criteria for the classication of bromyalgia: report of
the Multicenter Criteria Committee. Arthritis Rheum 1990;33:
160 72.
Geiger R, Strasak A, Treml B, Gasser K, Kleinsasser A, Fischer
V, et al. Six-minute walk test in children and adolescents.
J Pediatr 2007;150:3959.
Li AM, Yin J, Yu CC, Tsang T, So HK, Wong E, et al. The
six-minute walk test in healthy children: reliability and validity. Eur Respir J 2003;25:1057 60.
Reybrouck T, Weymans M, Stijns H, Knops J, van der Hauwaert L. Ventilatory anaerobic threshold in healthy children:
age and sex differences. Eur J Appl Physiol Occup Physiol
1985;54:278 84.
Weltman A, Katch VL. Relationship between the onset of
metabolic acidosis (anaerobic threshold) and maximal oxygen
uptake. J Sports Med Phys Fitness 1979;19:135 42.
Washington RL, van Gundy JC, Cohen C, Sondheimer HM,
Wolfe RR. Normal aerobic and anaerobic exercise data for
North American school-age children. J Pediatr 1988;112:223
33.
Schanberg LE, Sandborg C. Dyslipoproteinemia and premature atherosclerosis in pediatric systemic lupus erythematosus. Curr Rheumatol Rep 2004;6:42533.
Gazarian M, Feldman BM, Benson LN, Gilday DL, Laxer RM,
Silverman ED. Assessment of myocardial perfusion and function in childhood systemic lupus erythematosus. J Pediatr
1998;132:109 16.
Solway S, Brooks D, Lacasse Y, Thomas S. A qualitative
systematic overview of the measurement properties of functional walk tests used in the cardiorespiratory domain. Chest
2001;119:256 70.
Butland RJ, Pang J, Gross ER, Woodcock AA, Geddes DM.
Two-, six-, and 12-minute walking tests in respiratory disease.
Br Med J (Clin Res Ed) 1982;284:1607 8.
Minor MA, Johnson JC. Reliability and validity of a submaximal treadmill test to estimate aerobic capacity in women with
rheumatic disease. J Rheumatol 1996;23:151723.

545
44. Cooper DM, Weiler-Ravell D, Whipp BJ, Wasserman K.
Growth-related changes in oxygen uptake and heart rate during progressive exercise in children. Pediatr Res 1984;18:845
51.
45. Sakauchi M, Matsumura T, Yamaoka T, Koami T, Shibata M,
Nakamura M, et al. Reduced muscle uptake of oxygen during
exercise in patients with systemic lupus erythematosus.
J Rheumatol 1995;22:14837.
46. Valim V, Oliveira LM, Suda AL, Silva LE, Faro M, Neto TL, et
al. Peak oxygen uptake and ventilatory anaerobic threshold in
bromyalgia. J Rheumatol 2002;29:3537.
47. Davis JA, Vodak P, Wilmore JH, Vodak J, Kurtz P. Anaerobic
threshold and maximal aerobic power for three modes of
exercise. J Appl Physiol 1976;41:544 50.
48. Takken T, van der Net J, Helders PJ. Relationship between
functional ability and physical tness in juvenile idiopathic
arthritis patients. Scand J Rheumatol 2003;32:174 8.
49. Liang MH, Socher SA, Larson MG, Schur PH. Reliability and
validity of six systems for the clinical assessment of disease
activity in systemic lupus erythematosus. Arthritis Rheum
1989;32:110718.
50. De Carvalho MR, Sato EI, Tebexreni AS, Heidecher RT,
Schenkman S, Neto TL. Effects of supervised cardiovascular
training program on exercise tolerance, aerobic capacity, and
quality of life in patients with systemic lupus erythematosus.
Arthritis Rheum 2005;53:838 44.
51. Tench CM, McCarthy J, McCurdie I, White PD, DCruz DP.
Fatigue in systemic lupus erythematosus: a randomized controlled trial of exercise. Rheumatology (Oxford) 2003;42:
1050 4.
52. Daltroy LH, Robb-Nicholson C, Iversen MD, Wright EA, Liang
MH. Effectiveness of minimally supervised home aerobic
training in patients with systemic rheumatic disease. Br J
Rheumatol 1995;34:1064 9.
53. Robb-Nicholson LC, Daltroy L, Eaton H, Gall V, Wright E,
Hartley LH, et al. Effects of aerobic conditioning in lupus
fatigue: a pilot study. Br J Rheumatol 1989;28:500 5.
54. Ramsey-Goldman R, Schilling EM, Dunlop D, Langman C,
Greenland P, Thomas RJ, et al. A pilot study on the effects of
exercise in patients with systemic lupus erythematosus. Arthritis Care Res 2000;13:2629.
55. Clarke-Jenssen AC, Fredriksen PM, Lilleby V, Mengshoel AM.
Effects of supervised aerobic exercise in patients with systemic lupus erythematosus: a pilot study. Arthritis Rheum
2005;53:308 12.