Li Alemo Munters

Improved exercise performance and increased aerobic capacity after endurance training of patients with stable polymyositis and dermatomyositis

IntroductionThis randomized, controlled study on patients with polymyositis or dermatomyositis was based on three hypotheses: patients display impaired endurance due to reduced aerobic capacity and muscle weakness, endurance training improves their exercise performance by increasing the aerobic capacity, and endurance training has general beneficial effects on their health status.MethodsIn the first part of this study, we compared 23 patients with polymyositis or dermatomyositis with 12 age- and gender-matched healthy controls. A subgroup of patients were randomized to perform a 12-week endurance training program (exercise group, n = 9) or to a non-exercising control group (n = 6). We measured maximal oxygen uptake (VO2 max) and the associated power output during a progressive cycling test. Endurance was assessed as the cycling time to exhaustion at 65% of VO2 max. Lactate levels in the vastus lateralis muscle were measured with microdialysis. Mitochondrial function was assessed by measuring citrate synthase (CS) and β-hydroxyacyl-CoA dehydrogenase (β-HAD) activities in muscle biopsies. Clinical improvement was assessed according to the International Myositis Assessment and Clinical Studies Group (IMACS) improvement criteria. All assessors were blinded to the type of intervention (that is, training or control).ResultsExercise performance and aerobic capacity were lower in patients than in healthy controls, whereas lactate levels at exhaustion were similar. Patients in the exercise group increased their cycling time, aerobic capacity and CS and β-HAD activities, whereas lactate levels at exhaustion decreased. Six of nine patients in the exercise group met the IMACS improvement criteria. Patients in the control group did not show any consistent changes during the 12-week study.ConclusionsPolymyositis and dermatomyositis patients have impaired endurance, which could be improved by 12 weeks of endurance training. The clinical improvement corresponds to increases in aerobic capacity and muscle mitochondrial enzyme activities. The results emphasize the importance of endurance exercise in addition to immunosuppressive treatment of patients with polymyositis or dermatomyositis.Trial registrationClinicalTrials.gov: NCT01184625

Improvement in Health and Possible Reduction in Disease Activity Using Endurance Exercise in Patients With Established Polymyositis and Dermatomyositis : A Multicenter Randomized Controlled Trial With a 1-Year Open Extension Followup

To determine the effects of a 12‐week endurance exercise program on health, disability, VO2 max, and disease activity in a multicenter randomized controlled trial in patients with established polymyositis (PM) and dermatomyositis (DM), and to evaluate health and disability in a 1‐year open extension study.

Resistive Home Exercise in Patients with Recent-onset Polymyositis and Dermatomyositis — A Randomized Controlled Single-blinded Study with a 2-year Followup

Objective. To evaluate the outcome of resistive home exercise and its possible longterm influence on health, disability, and disease activity in patients with active polymyositis (PM) or dermatomyositis (DM). Methods. Nineteen patients with recent-onset PM/DM were included after introduction of high-dose prednisolone. They were assessed by independent assessors as to perceived health, muscle performance, aerobic capacity, and serum creatine phosphokinase (CPK) at baseline and after 24 weeks, including repeated muscle biopsies at 24 weeks (single-blinded randomized controlled study), and in an open-label followup at 52, 78, and 104 weeks. Patients were randomized to 12 weeks, 5 days/week resistive home exercise with telephone support and encouragement for another 12 weeks of twice-a-week home or gym exercise (EG, n = 10) or to 24 weeks, 5 days/week range of motion exercise (CG, n = 9). Patients in the CG group without inflammatory infiltrates in muscle biopsies at 24 weeks were invited to the 12-week resistive home exercises. Results. At baseline, the EG had poorer perceived health, but otherwise the groups were comparable. At 24 weeks, both groups improved in muscle performance and aerobic capacity (p < 0.001 to < 0.05) with no signs of increased inflammation assessed by CPK levels or muscle biopsies. Both groups improved in muscle performance and aerobic capacity up to 52 weeks (p < 0.05) lasting to 104 weeks in the EG (p < 0.05) and presented minor improvements in perceived health. Conclusion. Our study supports the safety of resistive exercise in patients with active PM/DM but did not reveal any between-group differences in exercise effects. An individually adapted physical therapist–supervised home exercise program might be recommended in early active PM/DM, with regular evaluation of muscle performance and health.

New Insights into the Benefits of Exercise for Muscle Health in Patients with Idiopathic Inflammatory Myositis

With recommended treatment, a majority with idiopathic inflammatory myopathy (IIM) develop muscle impairment and poor health. Beneficial effects of exercise have been reported on muscle performance, aerobic capacity and health in chronic polymyositis and dermatomyositis and to some extent in active disease and inclusion body myositis (IBM). Importantly, randomized controlled trials (RCTs) indicate that improved health and decreased clinical disease activity could be mediated through increased aerobic capacity. Recently, reports seeking mechanisms underlying effects of exercise in skeletal muscle indicate increased aerobic capacity (i.e. increased mitochondrial capacity and capillary density, reduced lactate levels), activation of genes in aerobic phenotype and muscle growth programs, and down regulation in genes related to inflammation. Altogether, exercise contributes to both systemic and within-muscle adaptations demonstrating that exercise is fundamental to improve muscle performance and health in IIM. There is a need for RCTs to study effects of exercise in active disease and IBM.

Patient Preference Assessment Reveals Disease Aspects Not Covered by Recommended Outcomes in Polymyositis and Dermatomyositis

Objectives. Polymyositis (PM) and dermatomyositis (DM) are characterized by impaired muscle function with a majority of patients developing sustained disability. The aim of this study was to evaluate the patients individual priorities (patient preference) of disabilities most important to improve in PM/DM using the MacMaster Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR), to correlate the MACTAR to myositis outcomes and to evaluate its test-retest reliability. Methods. Twenty-eight patients with PM/DM performed recommended outcomes as well as the MACTAR, which was performed twice with one week apart. Results. Sexual activity, walking, biking, social activities, and sleep constituted the predominating disabilities. Seventy-two and 33% of the identified disabilities were not covered by items of the Health Assessment Questionnaire and the Myositis Activities Profile. Correlations between the MACTAR and health-related quality of life measures were rs = −0.67–0.73, correlations with measures of activities of daily living and participation in society were rs = 0.51–0.60 with lower correlations for other outcomes. Intraclass correlation (ICC) and weighted Kappa (Kw) coefficients were 0.83 and 0.68, respectively, for test-retest reliability of the MACTAR. Conclusions. The MACTAR interview had promising measurement properties and identified patient preference disabilities in PM/DM that were not covered by recommended outcomes.

Endurance Exercise Improves Molecular Pathways of Aerobic Metabolism in Patients With Myositis

Endurance exercise demonstrates beneficial effects in polymyositis/dermatomyositis (PM/DM); however, the molecular effects of exercise on skeletal muscle are incompletely understood. We undertook this controlled pilot study to investigate the effects of a 12‐week endurance exercise training program on the molecular profile of skeletal muscle in patients with established PM/DM compared to a nonexercised control group of patients with established PM/DM.

Activated LTB4 pathway in muscle tissue of patients with polymyositis or dermatomyositis

Objective To investigate the involvement of the leukotriene B4 (LTB4) pathway in polymyositis (PM) and dermatomyositis (DM) and the effect of immunosuppressive treatment on the LTB4 pathway. Methods 5-lipoxygenase (5-LO), 5-LO activating protein (FLAP) and LTB4 receptor-1 (BLT1) expression was analysed by immunohistochemistry in muscle tissue from patients with PM/DM before and after immunosuppressive treatment and from healthy individuals. In vivo LTB4 in thigh muscle was measured by microdialysis at rest and after acute exercise in another cohort of patients and healthy controls. Results The number of 5-LO-positive cells and BLT1-positive capillaries was higher in patients with PM/DM than in healthy individuals. The number of FLAP-expressing cells divided the patients into two groups (high/low expression). Treatment reduced the number of FLAP-positive cells in the group with initial high levels, however the expression remained high compared with healthy individuals. The number of BLT1-positive cells was also reduced while staining for 5-LO was unchanged. An inverse correlation was observed between the number of 5-LO or FLAP-positive cells in muscle tissue and muscle performance. LTB4 could be detected in dialysate of muscle tissue in vivo in both patients and healthy controls and was significantly increased after exercise in patients. Conclusion The LTB4 pathway is upregulated in muscle tissue from patients with PM/DM and this upregulation correlated negatively to muscle performance, suggesting a role for LTB4 in myositis muscle weakness. The immunosuppressive treatment was insufficient on the LTB4 pathway and, for patients with high expression of FLAP, FLAP inhibitors may be considered as possible therapy.

Higher proportion of fast‐twitch (type II) muscle fibres in idiopathic inflammatory myopathies – evident in chronic but not in untreated newly diagnosed patients

Objective:  Polymyositis and dermatomyositis are idiopathic, inflammatory myopathies characterized by proximal muscle fatigue. Conventional immunosuppressive treatment gives a variable response. Biopsies from chronic patients display a low proportion type I and a high proportion of type II muscle fibres. This raised a suspicion that the low proportion of type I fibres might play a role in the muscle fatigue.

Disabilities of importance for patients to improve – using a patient preference tool in rheumatoid arthritis

Abstract Purpose: To investigate, using the McMaster Toronto Arthritis patient preference disability questionnaire (MACTAR), disabilities most important to improve in Swedish patients with rheumatoid arthritis (RA) and to compare these with the pre-defined activities in the International Classification of Functioning (ICF) comprehensive core set for RA and the Stanford Health Assessment Questionnaire (HAQ). Also to categorize patient preference selected disabilities using the ICF, to correlate the MACTAR score to RA core set measures and to evaluate the MACTAR’s test–retest reliability. Methods: 45 patients with RA (median (md) age 59 years, diagnosis duration md 10 years) were included. Assessments included disease activity score (DAS28), timed-stands test (TST), shoulder function assessment (SFA), visual analogue scale for pain (VAS), HAQ, patients’ global assessment of well-being (PGA) and the MACTAR. Results: 58 disabilities were identified of which 17 were identified by at least 5 patients. 47% of them were represented in the Comprehensive ICF RA core set and 53% in the HAQ. 16/17 were categorized in the ICF activities and participation component. Correlations between the MACTAR and other measures were: DAS28 (rs −0.65), TST (rs −0.19), SFA (rs 0.38), VAS (rs −0.61), HAQ (rs −0.51) and PGA (rs −0.61). Weighted κ was 0.59. Conclusions: Half of the disabilities patients with RA identified by use of the MACTAR are not evaluated in the Comprehensive ICF core set for RA or the HAQ. MACTAR has moderate test–retest reliability. MACTAR can be considered to be used in addition to traditional RA outcomes and may potentially improve clinical assessment of patients with RA. Implications for Rehabilitation RA has an impact on personal life areas. The MACTAR helps identify individual disease-related disabilities of importance to improve. The MACTAR provides an opportunity for individualized goal-setting in rehabilitation and can thus promote adherence in rehabilitation. MACTAR may potentially improve clinical assessment for patients with RA.

Effect of endurance exercise on microRNAs in myositis skeletal muscle-A randomized controlled study.

Objective To identify changes in skeletal muscle microRNA expression after endurance exercise and associate the identified microRNAs with mRNA and protein expression to disease-specific pathways in polymyositis (PM) and dermatomyositis (DM) patients. Methods Following a parallel clinical trial design, patients with probable PM or DM, exercising less than once a week, and on stable medication for at least one month were randomized into two groups at Karolinska University Hospital: a 12-week endurance exercise group (n = 12) or a non-exercised control group (n = 11). Using an Affymetrix microarray, microRNA expression was determined in paired muscle biopsies taken before and after the exercise intervention from 3 patients in each group. Ingenuity pathway analysis with a microRNA target filter was used to identify microRNA transcript targets. These targets were investigated at the mRNA (microarray) and protein (mass spectrometry) levels in patients. Results Endurance exercise altered 39 microRNAs. The microRNAs with increased expression were predicted to target transcripts involved in inflammatory processes, metabolism, and muscle atrophy. Further, these target transcripts had an associated decrease in mRNA expression in exercised patients. In particular, a decrease in the NF-κB regulator IKBKB was associated with an increase in its target microRNA (miR-196b). At the protein level, there was an increase in mitochondrial proteins (AK3, HIBADH), which were associated with a decrease in microRNAs that were predicted to regulate their expression. Conclusion Improvement in disease phenotype after exercise is associated with increasing microRNAs that target and downregulate immune processes at the transcript level, as well as decreasing microRNAs that target and upregulate mitochondrial content at the protein level. Therefore, microRNAs may improve disease by decreasing immune responses and increasing mitochondrial biogenesis. Trial registration ClinicalTrials.gov NCT01184625