Exploring the feasibility of an exercise programme including aerobic and resistance training in people with limited cutaneous systemic sclerosis.

OBJECTIVES: It is suggested that exercise can improve the vascular function and quality of life (QoL) in people with systemic sclerosis (SSc), potentially offering clinical benefits to this population. Yet the feasibility of such an intervention remains untested. Therefore, the purpose of this study is to examine the feasibility of a combined exercise protocol (aerobic and resistance training) in people with limited cutaneous SSc (lcSSc). METHODS: Thirty-two lcSSc patients (66.5 ± 12 years old) were randomly allocated in two groups (exercise and control group). The exercise group underwent a 12-week exercise programme, twice per week. All patients performed the baseline, three- and six-month follow-up measurements where functional ability, body composition and QoL were assessed. Participants' experiences were explored through interviews. RESULTS: Compliance was 92.6% with no dropouts. The individuals' confidence to participate in the study's exercise protocol for twice per week was 95%. The average value for the physical activity enjoyment scale was 103 ± 10 out of 119 (highest score). The mean values for the intention to engage in exercise twice per week were 6.4 ± 1 (likely) out of 7 (very likely). QoL for the exercise group showed to have a better life satisfaction, less anxiety and Raynaud's phenomenon-accompanied pain. CONCLUSIONS: Our results suggest that a combined exercise protocol was feasible for people with lcSSc, with no adverse events, resulting in high adherence and low attrition rates, high enjoyment levels and intentions for future engagement to this exercise. Thus, the specific protocol is a safe adjunct therapy for people with lcSSc. TRIAL REGISTRATION: ClinicalTrials.gov (NCT number): NCT03058887, February 23, 2017, https://clinicaltrials.gov/ct2/show/NCT03058887?term=NCT03058887&rank=1Key Points• High-intensity interval training in combination with resistance training constitutes a feasible exercise protocol for people with lcSSc.• Overall, the exercise programme demonstrated high adherence and enjoyment levels and low attrition rates.• The exercise protocol was proved to be safe with no adverse events for people with lcSSc

The Effects of Exercise on Vascular Physiology in Systemic Sclerosis Patients

The original research in this thesis aimed to investigate the efficacy and feasibility of exercise in people with systemic sclerosis (SSc). The heralding symptom in the pathophysiology of SSc is vascular dysfunction in the digital area which is the primary cause of Raynaud's phenomenon (RP). Digital disfiguration, ulcers and RP affect the quality of life (QoL) in people with SSc. Medical treatment does not have dramatic improvements and is also accompanied by short- and long-term side effects leading to further health complications. Exercise could be considered as a safe and cost-effective adjunct therapy that could potentially reduce the use of medication. The primary outcomes in study 1 were the physiological differences between the arm crank (ACE) and cycler ergometer (CE) protocols in sedentary adults. Study 2 investigated the microvascular function, quality of life, cardiorespiratory fitness, functional capacity and body composition in people with SSc. Study 3 explored the feasibility of exercise in people with SSc with primary outcomes being the recruitment and attrition rates as well as the adherence rates to exercise. The novel findings of this research were: Study's 1 novelty was 1) the predictive equation for the cycle ergometer peak oxygen uptake (CEV̇ O2peak) trough the physiological responses of ACE and body composition features (Study 1). The equation estimated with this model is: CEV̇ O2peak = 11.776 + 1.418 X arm crank ergometer peak oxygen uptake (ACEV̇ O2peak) (ml·kg-1·min-) – 1.454 x total lean body mass (TLBM) + 3.967 X lower limb lean body mass (LLLBM). This predictive equation was later used in study 2 to compare ACE to CE V̇ O2peak as a correlation between the improvement of microcirculation (laser-Doppler fluximetry) and V̇ O2peak has been demonstrated in rheumatoid arthritis patients before (Metsios et al., 2014). Study's 2 novelties were 2) ACE seems more potent to improve the microcirculation in the digital area in people with SSc compared to CE, 3) the exercise programme that consisted of a high intensity interval training (HIIT) protocol that was performed for 12 weeks twice per week seems capable to prevent the formation of digital ulcers in people with SSc and the concomitant hospitalisations and/or in some occasions digital amputations, 4) QoL in people with SSc significantly improved after the exercise intervention. Study's 3 novelties were that 5) the exercise programme (12 weeks, twice/week) was feasible in people with SSc with very high recruitment and adherence rates, 6) our combined exercise protocol (HIIT and resistance training) was enjoyable and fairly easy to be performed by our participants, 7) individuals experiences confirmed the feasibility of our intervention and exercise protocol and highlighting the importance of applying supervised exercise programmes. Study 2 acted as a guiding study as to which mode of exercise could induce better results in the microcirculation in the digital area. Afterwards, study 3 utilised the upper limb exercise with weight training to assess its feasibility in people with systemic sclerosis. These findings contribute to the growing evidence base for the effects of exercise in people with SSc. Our study is the first to investigate the effects of HIIT on digital microcirculation in people with SSc and the first to explore the feasibility of a combined exercise protocol in this clinical population. Future research should explore the effects of exercise in people with SSc in larger clinical trials

Validation of an arm crank ergometer test for use in sedentary adults

The maximal oxygen uptake (V̇O2peak) test is an approved pre-operative examination tool, in a clinical setting: Both V̇O2peak and anaerobic threshold indicate a patient's physiological tolerance for major surgery and post-operative mortality, with cycle ergometry being routinely used for V̇O2peak tests in clinical settings, in many European countries. Nevertheless, the opportunities to assess populations with restricted mobility of the lower limbs are limited, as alternative methods (such as an arm-crank test protocol) to assess V̇O2peak are yet to be established. Twelve sedentary middle-aged adults (55.1 ± 5.0 years) performed two incremental protocols on an arm crank and cycle ergometer on separate occasions. During exercise, gas exchange was collected and analysed by an online breath-by-breath analysis system. Regression analysis showed that the model with dependent variable cycle ergometer V̇O2peak (CEV̇O2peak) in ml·kg-1·min-1 and independent variables arm crank V̇O2peak (ACEV̇O2peak) in ml·kg-1·min-1, lean body mass lower limbs (LBMLL) and total lean body mass (TLBM) fitted the population the best, with r2 = 0.87, adj. r2 = 0.82 and SEE = 3.14. The equation estimated with this model is: CE V̇O2peak = 11.776 + 1.418 X ACE V̇O2peak(ml·kg-1·min-) – 1.454 x TLBM + 3.967 X LLLBM. Our study suggests that arm cranking could be an alternative mode of exercise for sedentary middle-aged adults (and potentially in clinical settings) to assess the cardiorespiratory fitness of people with restricted lower-limb mobility. Key words: Cardiopulmonary test, arm exercise, physiological responses, upper limbs

Exploring the microcirculatory effects of an exercise programme including aerobic and resistance training in people with limited cutaneous systemic sclerosis.

Purpose of the study High intensity interval training (HIIT) is able to improve the endothelial-dependent microvascular function is people with limited cutaneous systemic sclerosis (lcSSc). Resistance training (RT) alone has shown significant improvements in the function of the vasculature; moreover, a combination of aerobic and RT have shown both in the past and recently to significantly improve the vascular function and the microcirculation. Therefore, the purpose of this study is to explore the effectiveness of a combined exercise protocol (aerobic and resistance training) on microvascular function in people with lcSSc. Methods Thirty-two lcSSc patients (66.5 ± 12 years old) were randomly allocated in two groups (exercise and control group). The exercise group underwent a 12-week exercise programme twice per week. All patients performed the baseline, three- and six-month follow up measurements where microvascular function, transcutaneous oxygen tension (ΔTcpO2) and body composition were assessed. Results The time to peak endothelial-dependent reactivity was significantly improved (91 ± 42 s, d = 1.06, p = 0.007) when compared to control group after the exercise intervention. Endothelial-independent function was also significantly improved (3.16 ± 2, d = 1.17, p = 0.005) when compared to the control group. Baseline (5.71 ± 4.4, p < 0.05)) and peak (15.4 ± 7.5, p < 0.05) transcutaneous oxygen pressure were also significantly improved compared to the control group. Conclusions Our results suggest that a combined exercise protocol (aerobic and RT) was effective in improving endothelial-dependent reactivity in people with lcSSc. The next step would be to explore its clinical- and cost- effectiveness. Therefore, we recommend a large, community-based intervention against standard pharmacotherapy only, which would assess these important factors and support a change in therapeutic protocols and guidelines for this clinical population

Detection and diagnosis of large airway collapse: a systematic review

Large airway collapse (LAC) is a frequently encountered clinical problem, caused by tracheobronchomalacia +/− excessive dynamic airway collapse, yet there are currently no universally accepted diagnostic criteria. We systematically reviewed studies reporting a diagnostic approach to LAC in healthy adults and patients, to compare diagnostic modalities and criteria used. Electronic databases were searched for relevant studies between 1989 and 2019. Studies that reported a diagnostic approach using computed tomography (CT), magnetic resonance imaging or flexible fibreoptic bronchoscopy were included. Random effects meta-analyses were performed to estimate the prevalence of LAC in healthy subjects and in patients with chronic obstructive airway diseases. We included 41 studies, describing 10 071 subjects (47% female) with a mean±sd age of 59±9 years. Most studies (n=35) reported CT findings, and only three studies reported bronchoscopic findings. The most reported diagnostic criterion was a ≥50% reduction in tracheal or main bronchi calibre at end-expiration on dynamic expiratory CT. Meta-analyses of relevant studies found that 17% (95% CI: 0–61%) of healthy subjects and 27% (95% CI: 11–46%) of patients with chronic airways disease were classified as having LAC, using this threshold. The most reported approach to diagnose LAC utilises CT diagnostics, and at a threshold used by most clinicians (i.e.≥50%) may classify a considerable proportion of healthy individuals as being abnormal and having LAC in a quarter of patients with chronic airways disease. Future work should focus on establishing more precise diagnostic criteria for LAC, relating this to relevant physiological and disease sequelae

Detection and diagnosis of large airway collapse: a systematic review

Large airway collapse (LAC) is a frequently encountered clinical problem, caused by tracheobronchomalacia +/− excessive dynamic airway collapse, yet there are currently no universally accepted diagnostic criteria. We systematically reviewed studies reporting a diagnostic approach to LAC in healthy adults and patients, to compare diagnostic modalities and criteria used. Electronic databases were searched for relevant studies between 1989 and 2019. Studies that reported a diagnostic approach using computed tomography (CT), magnetic resonance imaging or flexible fibreoptic bronchoscopy were included. Random effects meta-analyses were performed to estimate the prevalence of LAC in healthy subjects and in patients with chronic obstructive airway diseases. We included 41 studies, describing 10 071 subjects (47% female) with a mean±sd age of 59±9 years. Most studies (n=35) reported CT findings, and only three studies reported bronchoscopic findings. The most reported diagnostic criterion was a ≥50% reduction in tracheal or main bronchi calibre at end-expiration on dynamic expiratory CT. Meta-analyses of relevant studies found that 17% (95% CI: 0–61%) of healthy subjects and 27% (95% CI: 11–46%) of patients with chronic airways disease were classified as having LAC, using this threshold. The most reported approach to diagnose LAC utilises CT diagnostics, and at a threshold used by most clinicians (i.e.≥50%) may classify a considerable proportion of healthy individuals as being abnormal and having LAC in a quarter of patients with chronic airways disease. Future work should focus on establishing more precise diagnostic criteria for LAC, relating this to relevant physiological and disease sequelae

Right Ventricular Morphology and Function after Exercise Training in People with Systemic Sclerosis: A Randomized Controlled Pilot Study.

Background: Vascular dysfunction and its concomitant multi-organ involvement, including cardiac involvement, affects prognosis in systemic sclerosis (SSc) patients. Regular exercise has demonstrated to be able to improve vascular function in SSc. However, the effects of an exercise program on the heart and specifically in right ventricular (RV) morphology and function in SSc have yet to be explored. The study aimed to examine whether a 3-month combined exercise program can affect RV morphology and function in SSc patients. Methods: Twenty-eight SSc patients were randomly allocated to either the exercise training (ET) or the control (CON) group. Baseline and follow-up assessments consisted of a cardiopulmonary exercise test along with both a conventional and a two-dimensional speckle tracking echocardiography (2DSTE) focused on RV morphology and function. Following the baseline assessments, Group ET participated in a supervised combined exercise program for 12 weeks, while group CON received their usual care. Results: The ET group demonstrated increases in peak oxygen consumption by 25.1% (p < 0.001), global RV free wall longitudinal systolic strain by 6.69% (p < 0.03), RV free wall longitudinal systolic strain of the basal segment by 13.5% (p < 0.001), and global RV four-chamber longitudinal systolic strain by 6.76% (p < 0.03) following the exercise program. No differences were observed in group CON. Conclusions: Combined exercise improved cardiorespiratory efficiency and indices of RV systolic function, as assessed by the 2DSTE, in SSc patients

Investigating the effectiveness and feasibility of exercise on microvascular reactivity and quality of life in systemic sclerosis patients: study protocol for a feasibility study

Background: Raynaud’s phenomenon is one of the first clinical manifestations observed in systemic sclerosis (SSc). This microvasculature disorder affects mostly the digits in over 95% of SSc patients, significantly affecting their healthrelated quality of life (HRQoL) and incurring higher hospital admissions and other healthcare costs. Exercise is known to improve both micro- and macrovascular function – aerobic exercise and resistance training, separately or combined, have been demonstrated to lead to significant vasculo-physiological improvements in conditions that present vasculopathy. However, the effects of a combined exercise programme on microcirculation in SSc patients has yet to be investigated. Therefore, the purpose of this study is to assess the effects of high-intensity interval training (HIIT) combined with circuit resistance training on the microvascular function in the digital area of SSc patients. Methods: This will be a randomised controlled, feasibility trial with two arms, wherein 30 patients with SSc in receipt of medical treatment will be randomly assigned to usual care (medical treatment) or to a 12-week supervised exercise programme. Patients in the exercise group will undertake two, 45-min sessions each week consisting of 30 min HIIT (30 s 100% peak power output/30 s passive recovery) on the arm crank ergometer and 15 min of upper body circuit resistance training. Patients will be assessed before as well as at 3 and 6 months following randomisation. Primary outcomes of the study will be recruitment and retention rate, intervention acceptability and adherence to the exercise programme. Secondary outcomes include the digital area cutaneous microvascular function (laser Doppler fluximetry combined with iontophoresis), physical fitness, functional ability, upper back transcutaneous oxygen tension, body composition and quality of life (EQ-5D-5L). Selected interviews with a subsample of patients will be undertaken to explore their experiences of having Raynaud’s phenomenon and the acceptability of the exercise intervention and study procedures. Discussion: Data from this study will be used to identify the feasibility of a combined exercise programme to be implemented in SSc patients, the acceptability of the intervention and the study design, and to determine the effects of exercise on the microvasculature. Overall, this study will provide sufficient data to inform and support a full multicentre clinical trial

EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis

Objective To develop evidence-based recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Methods A task force comprising 7 rheumatologists, 15 other healthcare professionals and 3 patients was established. Following a systematic literature review performed to inform the recommendations, statements were formulated, discussed during online meetings and graded based on risk of bias assessment, level of evidence (LoE) and strength of recommendation (SoR; scale A–D, A comprising consistent LoE 1 studies, D comprising LoE 4 or inconsistent studies), following the European Alliance of Associations for Rheumatology standard operating procedure. Level of agreement (LoA; scale 0–10, 0 denoting complete disagreement, 10 denoting complete agreement) was determined for each statement through online voting. Results Four overarching principles and 12 recommendations were developed. These concerned common and disease-specific aspects of non-pharmacological management. SoR ranged from A to D. The mean LoA with the overarching principles and recommendations ranged from 8.4 to 9.7. Briefly, non-pharmacological management of SLE and SSc should be tailored, person-centred and participatory. It is not intended to preclude but rather complement pharmacotherapy. Patients should be offered education and support for physical exercise, smoking cessation and avoidance of cold exposure. Photoprotection and psychosocial interventions are important for SLE patients, while mouth and hand exercises are important in SSc. Conclusions The recommendations will guide healthcare professionals and patients towards a holistic and personalised management of SLE and SSc. Research and educational agendas were developed to address needs towards a higher evidence level, enhancement of clinician–patient communication and improved outcomes

EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis

Objective To develop evidence-based recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Methods A task force comprising 7 rheumatologists, 15 other healthcare professionals and 3 patients was established. Following a systematic literature review performed to inform the recommendations, statements were formulated, discussed during online meetings and graded based on risk of bias assessment, level of evidence (LoE) and strength of recommendation (SoR; scale AD , A comprising consistent LoE 1 studies, D comprising LoE 4 or inconsistent studies), following the European Alliance of Associations for Rheumatology standard operating procedure. Level of agreement (LoA; scale 0-10, 0 denoting complete disagreement, 10 denoting complete agreement) was determined for each statement through online voting. Results Four overarching principles and 12 recommendations were developed. These concerned common and disease-specific aspects of non-pharmacological management. SoR ranged from A to D. The mean LoA with the overarching principles and recommendations ranged from 8.4 to 9.7. Briefly, non-pharmacological management of SLE and SSc should be tailored, person-centred and participatory. It is not intended to preclude but rather complement pharmacotherapy. Patients should be offered education and support for physical exercise, smoking cessation and avoidance of cold exposure. Photoprotection and psychosocial interventions are important for SLE patients, while mouth and hand exercises are important in SSc. Conclusions The recommendations will guide healthcare professionals and patients towards a holistic and personalised management of SLE and SSc. Research and educational agendas were developed to address needs towards a higher evidence level, enhancement of clinician-patient communication and improved outcomes