Abstract
Objective. To investigate the effect of a moderate to high intensive exercise program on two primary outcomes (aerobic capacity, fatigue), and three secondary outcomes [anxiety, depression and health-related quality of life (HRQoL)] in women with primary Sjögren's syndrome (primary SS).
Methods. Twenty-one women with primary SS were ranked according to degree of fatigue and allocated to an exercise group (TG; n = 11) or a control group (CG; n = 10). The exercise method was Nordic walking for 45 min three times a week for 12 weeks. Outcome measures assessed at baseline and after 12 weeks were aerobic capacity, fatigue, ratings of perceived exertion (RPE), anxiety, depression and HRQoL.
Results. Nine women in the TG and 10 women in the CG completed the study. Analysis showed significant differences between the groups regarding aerobic capacity ( P = 0.03), fatigue ( P = 0.03), RPE ( P = 0.03), and depression ( P = 0.02) with the better values for the TG. There were no differences in anxiety or HRQoL.
Conclusion. Our findings support the use of appropriate aerobic exercise in the treatment of primary SS.
Introduction
Fatigue is a common symptom in rheumatic diseases [ 1 , 2 ] and is one of the most frequent non-exocrine complaints in primary Sjögren's syndrome (primary SS) [ 3 ]. Factors associated with fatigue in rheumatic diseases are sleep disturbances [ 4 ], disease activity, pain, anxiety, depression and decreased level of physical activity [ 5 ]. Aerobic capacity has been reported to be reduced in rheumatic diseases including primary SS [ 6–8 ]. It has also been indicated that fatigue is related to reduced aerobic capacity in women with primary SS [ 8 ]. Reduced fatigue after aerobic exercise therapy has earlier been described in rheumatic diseases [ 7 , 9 , 10 ] but not, as far as we know, in primary SS.
The purpose of this controlled clinical trial was to investigate whether (i) aerobic capacity and fatigue, and (ii) anxiety, depression and health-related quality of life (HRQoL) would benefit from a 12-week exercise programme in women with primary SS.
Patients and methods
Power calculation
Based on the results of a previous study [ 10 ] of exercise therapy and systemic lupus erythematosus (SLE), we expected a mean increase in VO 2max of 3.8 ml/kg/min and a s.d . of 2.76 in the exercise group (TG). No difference was expected in the control group (CG). Based on this, a sample size of ten in each group would be required to enable detection of a significant difference between groups with 80% power.
Patients
Inclusion criteria for participation in the study were: (i) female gender and age ≤67 yrs; (ii) primary SS diagnosed according to the American European Consensus Criteria (AECC) [ 11 ] and (iii) living in a specific area of southern Sweden. The exclusion criteria were: (i) use of beta-blocker therapy, or (ii) disease manifestations known to prevent or limit exercise performance. A total of 94 patients were recruited and 26 agreed to participate. Sixty women were limited to participate or declined participation, and eight women did not answer the invitation. The mean age of the 68 women who did not participate was 52 (24–67) yrs.
Of the 26 women who agreed to participate, 21 women remained for the intervention after the assessments. None of the patients had concomitant disease manifestations, and none were on medication that would limit exercise performance. The characteristics of the study population (those who completed the study) are presented in Table 1 .
Demographic and clinical characteristics, at baseline, and between group comparison of the median differences of the effect variables after 12 weeks exercise of the 9 women in the treatment group (TG) and the 10 women in the control group (CG) who completed the study
| Treatment group (TG) | Control group (CG) | ||
|---|---|---|---|
| ( n = 9) | ( n = 10) | ||
| Median (range) | Median (range) | P | |
| Characteristics | |||
| Age (years) | 60 (41–65) | 56.5 (42–63) | 0.02 |
| Years since clinical diagnosis | 5 (2–14) | 8 (3–23) | 0.21 |
| BMI | 28 (23–32) | 25.5 (21–36) | 0.56 |
| No. married or cohabiting | 6 | 9 | 0.21 |
| Years of education | 12 (8–15) | 13.5 (6–19) | 0.66 |
| No. working/not working a | 2/7 | 5/5 | 0.21 |
| No. of smokers | 0 | 0 | |
| Fatigue (ProF) | 54 (23–108) | 62.5 (16–99) | 0.72 |
| Fatigue (VAS) | 58 (19–80) | 66.5 (36–83) | 0.24 |
| Aerobic capacity, VO 2max l/min | 1.6 (1.3–2.2) | 1.75 (1.3–2.4) | 0.44 |
| Aerobic capacity, VO 2max (ml/kg/min) | 24 (17–33) | 25 (17–34) | 0.72 |
| No. physically active | 7 | 7 | |
| Musculoskeletal pain (VAS) | 43.5 (16–72) n=8 | 68 (15–75) n=7 | 0.52 |
| Haemoglobulin | 136 (120–159) | 136 (123–152) | 0.78 |
| CRP | 3 (2–9) | 2 (2–24) | 0.96 |
| CK | 1.5 (1–3.3) | 1.45 (0.8–2.2) | 0.45 |
| Between group comparison of the median changes after intervention | |||
| Fatigue (VAS), mm | −17 (−41–39) | 1.5 (−15–23) | 0.03 |
| Fatigue (ProF), total scale | −6 (−31–9) | −6 (−20–16) | 0.51 |
| Somatic fatigue (ProF) | −0.67 (−2–0.38) | −0.28 (−1.17–0.75) | 0.31 |
| Mental fatigue (ProF) | −0.5 (−3–1.25) | −0.25 (−2.25–1.25) | 0.62 |
| Aerobic capacity, VO 2max , l/min | 0.2 (−0.1–0.6) | 0 (−0.3–0.3) b | 0.03 |
| Aerobic capacity, VO 2max, ml/kg/min | 3 (−1–8) | 0 (−6–5) b | 0.06 |
| RPE | −1 (−3–1) | 1 (−2–2) | 0.03 |
| Anxiety (HADS) | −1 (−5–1) | −1 (−5–2) | 0.87 |
| Depression (HADS) | −2 (−4–1) | 0.5 (−2–4) | 0.02 |
| SF-36, subscale | |||
| Physical functioning | 15 (0–45) | 0 (−15–25) | 0.14 |
| Role, physical | 0 (−25–50) c | 0 (−50–50) | 0.61 |
| Bodily pain | 0 (−22–21) | 0 (−22–59) | 0.97 |
| General health | 5 (−15–25) | −5 (−17–17) | 0.25 |
| Vitality | 10 (−25–25) | 7.5 (−10–30) | 0.93 |
| Social functioning | 0 (−25–25) | 0 (−50–25) | 0.58 |
| Role, emotional | 0 (−33–100) c | 0 (−100–100) | 0.74 |
| Mental health | −4 (−24–4) | −4 (−16–24) | 0.30 |
| Treatment group (TG) | Control group (CG) | ||
|---|---|---|---|
| ( n = 9) | ( n = 10) | ||
| Median (range) | Median (range) | P | |
| Characteristics | |||
| Age (years) | 60 (41–65) | 56.5 (42–63) | 0.02 |
| Years since clinical diagnosis | 5 (2–14) | 8 (3–23) | 0.21 |
| BMI | 28 (23–32) | 25.5 (21–36) | 0.56 |
| No. married or cohabiting | 6 | 9 | 0.21 |
| Years of education | 12 (8–15) | 13.5 (6–19) | 0.66 |
| No. working/not working a | 2/7 | 5/5 | 0.21 |
| No. of smokers | 0 | 0 | |
| Fatigue (ProF) | 54 (23–108) | 62.5 (16–99) | 0.72 |
| Fatigue (VAS) | 58 (19–80) | 66.5 (36–83) | 0.24 |
| Aerobic capacity, VO 2max l/min | 1.6 (1.3–2.2) | 1.75 (1.3–2.4) | 0.44 |
| Aerobic capacity, VO 2max (ml/kg/min) | 24 (17–33) | 25 (17–34) | 0.72 |
| No. physically active | 7 | 7 | |
| Musculoskeletal pain (VAS) | 43.5 (16–72) n=8 | 68 (15–75) n=7 | 0.52 |
| Haemoglobulin | 136 (120–159) | 136 (123–152) | 0.78 |
| CRP | 3 (2–9) | 2 (2–24) | 0.96 |
| CK | 1.5 (1–3.3) | 1.45 (0.8–2.2) | 0.45 |
| Between group comparison of the median changes after intervention | |||
| Fatigue (VAS), mm | −17 (−41–39) | 1.5 (−15–23) | 0.03 |
| Fatigue (ProF), total scale | −6 (−31–9) | −6 (−20–16) | 0.51 |
| Somatic fatigue (ProF) | −0.67 (−2–0.38) | −0.28 (−1.17–0.75) | 0.31 |
| Mental fatigue (ProF) | −0.5 (−3–1.25) | −0.25 (−2.25–1.25) | 0.62 |
| Aerobic capacity, VO 2max , l/min | 0.2 (−0.1–0.6) | 0 (−0.3–0.3) b | 0.03 |
| Aerobic capacity, VO 2max, ml/kg/min | 3 (−1–8) | 0 (−6–5) b | 0.06 |
| RPE | −1 (−3–1) | 1 (−2–2) | 0.03 |
| Anxiety (HADS) | −1 (−5–1) | −1 (−5–2) | 0.87 |
| Depression (HADS) | −2 (−4–1) | 0.5 (−2–4) | 0.02 |
| SF-36, subscale | |||
| Physical functioning | 15 (0–45) | 0 (−15–25) | 0.14 |
| Role, physical | 0 (−25–50) c | 0 (−50–50) | 0.61 |
| Bodily pain | 0 (−22–21) | 0 (−22–59) | 0.97 |
| General health | 5 (−15–25) | −5 (−17–17) | 0.25 |
| Vitality | 10 (−25–25) | 7.5 (−10–30) | 0.93 |
| Social functioning | 0 (−25–25) | 0 (−50–25) | 0.58 |
| Role, emotional | 0 (−33–100) c | 0 (−100–100) | 0.74 |
| Mental health | −4 (−24–4) | −4 (−16–24) | 0.30 |
a Working: working part-time or full-time; not working: retired, on sick leave, or unemployed.
bn = 9, cn = 8.
P -values determined by Mann–Whitney U-test and χ 2 -test.
BMI, body mass index; VAS, Visual Analogue Scale (0–100, with 0 = no fatigue/no pain at all); ProF, Profile of Fatigue (0–112, somatic fatigue 0–7, mental fatigue 0–7, with 0 = no problem at all); VO 2max , maximal oxygen consumption; RPE, ratings of perceived exertion (6–20 with 6 = lightest exertion); HADS, Hospital Anxiety and Depression Scale (anxiety 0–21, depression 0–21, with 0 = no anxiety/depression); SF-36: Medical Outcome Study Short-Form 36 (0–100 with 0 = lowest level of health).
Study design
The study was a controlled intervention trial with two exercise programmes. One group, the TG, did medium to high-intensity aerobic exercises and the other group, the CG, did low-intensity home exercises. To balance the patient allocation to any of the two groups, patients were ranked by fatigue as measured by the Profile of Fatigue (ProF) [ 12 ]; see below. Patients with odd numbers were allocated to the TG and patients with even numbers were allocated to the CG. Thus, the allocation was 11 patients to TG and 10 patients to CG.
Exercise prescription
Treatment group (TG)
The exercise method was Nordic walking, which is walking with specially constructed ski poles. The TG met once a week for 12 consecutive weeks for a 45-min walk, and were instructed to walk for 45 min twice more every week at home. All participants were provided with walking poles and a telemetric heart rate monitor. The weekly group sessions were conducted by a trained walker. During the first 8 weeks the patients were told to exercise at a heart rate corresponding to 60–70% of age-predicted maximum heart rate and for the remaining 4 weeks they were told to exercise at 70–80% of age-predicted maximum heart rate. Age-predicted maximum heart rate was estimated to be 220 minus the age of the individual. Logs of exercise duration, average heart rate and perceived exertion were kept by the patient.
Control group (CG)
The 10 patients in the CG were given written instructions for range of motion exercises to be performed at home three times a week over 12 weeks. Otherwise, the patients were told to maintain their current level of activity during the 12-week programme. The patients kept exercise logs.
Assessment methods
Assessments were done before and immediately after the exercise period of 12 weeks. The patients completed a questionnaire regarding back ground data, fatigue, anxiety, depression and HRQoL. After this, the bicycle test was performed.
Fatigue was measured with the validated Swedish version of the disease-specific Profile of Fatigue questionnaire (ProF) [ 12 ]. It consists of 16 items evaluating somatic fatigue and mental fatigue: the somatic domain (12 items) and the mental domain (four items). The scoring for the items is 0–7, with 0 labelled ‘no problem at all’, and the calculated total score for the 16 items is 112. The scoring for each domain is transferred into a 0–7 scale. The scoring of the instrument has been carefully described elsewhere [ 12 ].
Fatigue was also assessed by a 100-mm visual analogue scale (VAS) where 0 was defined as ‘not fatigued at all’ and 100 as ‘extremely fatigued’.
Aerobic capacity
The method of Åstrand [ 13 ] was used to calculate the maximum oxygen uptake (VO 2max ). A single observer, blinded as to the allocation, conducted the bicycle tests. At the end of every minute during the test, general exertion was rated on the Borg RPE (ratings of perceived exertion) scale [ 14 ]. The RPE score of the last minute of the bicycle test was registered. The range of the RPE scale is 6–20, where 6 means no exertion at all and 20 means maximal exertion.
Health-related quality of life was measured with the Swedish version of the self-administered Short Form 36 (SF-36) [ 15 ]. This is a generic instrument composed of eight subscales assessing different dimensions of HRQoL including both physical and mental health. The scaling ranges from 0 to 100 and higher values indicate better health.
Anxiety and depression
The Hospital Anxiety and Depression scale (HADS) [ 16 ] has been constructed to assess anxiety and depression in patients with somatic diseases. It contains 14 items for self-assessment on a scale from 0 to 3. Seven items are intended to measure anxiety and seven depression, independently of each other, and the entire scale ranges from 0 to 21 each for anxiety and depression. A score of 8–10 on a subscale represents possible psychiatric morbidity and a score of more than 10 represents clinical anxiety or depression [ 16 ].
Statistics
The descriptive results are presented as median and range. Mann–Whitney U test and chi-squared test were used in comparisons between groups. Intention to treat analysis was performed for evaluation of the results of aerobic capacity (VO 2max l/min, VO 2max ml/kg/min). One patient in the CG did not manage to complete the bicycle test due to exhaustion after the 12 weeks, and was therefore given the same value as the worst performed by the study participants of the two groups. One patient in the CG could not perform the bicycle test at follow-up due to osteoarthritis of the knee, and was excluded from the analysis of aerobic capacity. Wilcoxon matched pairs signed rank sum test was used in comparisons within groups. The significance level was set at P ≤ 0.05.
Ethics
The medical ethics committee of Lund University approved the design of the study (approval no. LU-51-03).
Results
Drop-outs
Nine patients in the TG and ten patients in the CG completed the study. One patient in the TG was wrongly included due to misdiagnosis of her condition (protocol violation) and one patient in the TG dropped out during the training period due to family matters.
Compliance
The median number of exercise sessions in the TG during the 12 weeks was 35 (24–47). The median number of supervised sessions attended by the participants in the TG was 8 (7–12). The median number of home exercise sessions in the CG was 38 (30–80).
Between-group comparisons
The results of the between-group analyses are given in Table 1 .
Fatigue was significantly reduced in the TG, as measured with VAS ( P = 0.03). No reduction of fatigue was seen according to the ProF.
Aerobic capacity
In the TG, significant improvement was seen in VO 2max l/min ( P = 0.03) and the improvement in VO 2max ml/kg/min almost reached statistical significance ( P = 0.06).
There was no correlation between changes in VAS fatigue and in aerobic capacity.
There was a significant improvement in the TG in the RPE-scale ( P = 0.03). The individual changes in fatigue and aerobic capacity are seen in Fig. 1 .
Individual changes in fatigue (VAS, mm) and aerobic capacity (VO 2max ml/kg/min) in the treatment group and the control group after 12 weeks.
Individual changes in fatigue (VAS, mm) and aerobic capacity (VO 2max ml/kg/min) in the treatment group and the control group after 12 weeks.
Health-related quality of life
No differences were seen in any of the eight dimensions of SF-36 in comparisons between the TG and the CG.
Anxiety and depression
The depression score was significantly lower in the TG ( P = 0.02), whereas no difference between the groups was seen in anxiety.
Within-group comparisons
The TG improved significantly in VO 2max l/min ( P = 0.03); VO 2max ml/kg/min ( P = 0.02), RPE ( P = 0.05), depression ( P = 0.02), and the physical function subscale of SF-36 ( P = 0.01). A deterioration was seen in the mental health subscale of SF-36 ( P = 0.03). There were no differences in any of the outcome measures within the CG.
Discussion
The main purpose of the present study was to investigate the effect on aerobic capacity and fatigue of an exercise programme in women with primary SS. To the authors’ knowledge, this is the first study on this subject dealing with primary SS. The key findings in our study are that regular episodes with Nordic walking over 12 weeks improved aerobic capacity and reduced fatigue in these patients. Many studies have been conducted in rheumatic diseases to evaluate the effect of exercise on aerobic capacity [ 17 ]. Some studies have also described the effects of exercise on fatigue, and the results of these support the findings of our study [ 7 , 9 , 10 ].
Although the depression score at baseline did not represent psychiatric morbidity, the difference in the depression score was significant in the TG compared with the CG after the exercise period. The effect of exercise programmes in reducing symptoms of depression have been reported for other rheumatic disorders [ 18 ].
Fatigue was assessed with two different instruments, the VAS and the ProF. Only one of these, the VAS, detected a difference between the groups. The SF-36 vitality scale, which assesses the opposite of fatigue and may be regarded as a measure of fatigue, did not change either. The reason for this may be lack of statistical power of the ProF and the SF-36 vitality scale to detect a change due to too few participants. All three instruments are valid for the measurement of fatigue. However, the VAS may be the most sensitive. It may also capture additional dimensions. Better sensitivity to change of the VAS than multidimensional scales in the assessment of fatigue in RA has been reported [ 19 ].
The lacking correlation between change in fatigue and in aerobic capacity in the TG was unexpected. Chronic fatigue may have a central origin, i.e. dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis [ 20 ]. The underlying mechanism by which fatigue benefits from exercise is, as fatigue itself, poorly understood. Influence on the HPA-axis may be one explanation.
A limiting factor in our study is the small sample size, with just 9 and 10 participants who completed the study in each group. Of those who answered the invitation and fulfilled the inclusion criteria ( n = 63), 59% ( n = 37) declined participation. The majority of those who volunteered were relatively old and were mainly unemployed. This suggests a selection bias and limits the generalizability of the study. Another limitation is the lack of a long-term follow-up of the exercise effects.
In summary, despite the small sample size, we found significant improvements in primary outcomes, aerobic capacity and fatigue (as measured with VAS) after a 12-week aerobic exercise programme. We also found a reduced depression score. This suggests that an aerobic exercise programme should be part of the management of primary SS.
The authors have declared no conflicts of interest.
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