Physical Activity and Sedentary Behaviour in People with Myasthenia Gravis: A Cross-Sectional Study

INTRODUCTION

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease involving dysfunction at the neuromuscular junction resulting in fatigue and muscle weakness, presenting as either ocular or generalised weakness [1]. Despite increasing life expectancy and availability of treatments [2], people with MG continue to experience reduced health-related quality of life [3–6]. Impairments such as fatigue [5–8] and walking limitation [9] have been reported in people with MG, with interest growing in whether balance is also impaired [10, 11].

Historically, advice regarding physical activity has been conservative in people with MG given uncertainty as to the impact of activities on weakness and fatigue [12, 13]. Evidence now indicates exercise is feasible, safe and effective in improving outcomes and disease processes [14] in people with MG; specifically exercises targeting balance [15], strength and aerobic capacity [16–19]. Additionally, improvements have been noted in walking distance (as measured by the 6-minute walk test) following various exercise interventions incorporating strength and aerobic exercises [18–20]. Structured exercise offers opportunity for persons with MG to improve specific impairments and fitness, however, it is only one component of the broader concept of physical activity.

Physical activity and time spent sedentary (activities performed while awake in a sitting or lying position with an energy expenditure of < 1.5 METs; metabolic equivalents) [21] are important determinants of health [22]. METs are a measure of energy cost, with 1 MET equating to the energy expended at rest and ≥3 METs classified as moderate-vigorous physical activity (MVPA) [23]. Global public health guidelines recommend that in order to attain health benefits, individuals should attain sufficient physical activity (a minimum of 150 minutes of MVPA per week) and minimise time in prolonged sitting or lying during waking hours [24, 25]. A combination of higher levels of physical activity and lower time spent sedentary is associated with reduced mortality, reduced occurrence of non-communicable diseases and improved quality of life [22, 26], with increasing levels of physical activity demonstrated to mitigate the effects of sedentary behavior [27].

There is increasing but limited research into habitual physical activity and sedentary behaviour in people with MG. Previous cross-sectional studies with relatively small sample sizes (n = 10–33) found that most participants were sufficiently physically active, however, engaged in minimal vigorous activity and had high levels of sedentary time [18, 28–30]. More recent, larger studies (n = 779 and 69, respectively) found that between 47–54%of participants were sufficiently active [8, 31]. These studies also investigated associations between these health behaviours and several relevant outcomes. For example, lower levels of physical activity have been associated with reduced 6-minute walk test distance [28], higher fatigue and reduced health-related quality of life [8]. Additionally, negative associations have been found between physical activity and body mass index (BMI) [8, 28], age, disease severity [31] and number of comorbidities [8]. However, these findings are in conflict with other studies that did not find such associations, for example with disease severity [28, 29] and health-related quality of life [28]. Similarly, sedentary time has been positively associated with disease severity [31] and negatively associated with BMI [28]. However, these findings are conflicting between studies [28, 31]. Further research is required to better understand these health behaviours and their potential associations given variability between studies. Given the positive effects of physical activity and the negative effects of being insufficiently physically active and engaging in higher sedentary time [27, 32], these behaviours, and specifically the combined impact of these behaviours, warrant further investigation to ensure people with MG are receiving evidence-based advice to optimise health and wellbeing outcomes.

The aim of this cross-sectional study was to describe the patterns of self-reported physical activity and sedentary behaviour in adults with MG and to explore associations between these health-related behaviours and self-reported fatigue, quality of life, walking limitation and balance confidence.

MATERIALS AND METHODS

RESULTS

Participant demographics and clinical characteristics are presented in Table 1 and descriptive statistics for physical activity, sedentary behaviour, fatigue, quality of life, walking limitation and balance confidence are presented in Table 2. Eighty-five participants (74%female) with an average age of 48±15.52 years completed the survey. 87%(n = 74) of participants were ambulant without a mobility aid. Around two-thirds of participants (n = 53, 62.4%) were sufficiently active according to physical activity guidelines [25] and over a third (n = 36, 42.4%) reported spending ≥10 h/day sedentary.

Associations between physical activity and sedentary behaviour and fatigue, quality of life, walking limitation and balance confidence are reported in Table 3. Physical activity was significantly negatively associated with fatigue, quality of life and walking limitation, and positively associated with balance confidence (R² 0.196–0.330). Thus, sufficiently active participants reported reduced fatigue, higher quality of life, less walking limitation and greater balance confidence. Sedentary behaviour was not significantly associated with any of the outcomes.

Associations between patterns of physical activity and sedentary behaviour and the outcomes measured are reported in Table 4. Compared with the reference group (those who were sufficiently active and spent < 10 h/day sedentary), fatigue was significantly higher, quality of life was significantly lower and walking limitation was significantly greater in the insufficiently active groups (regardless of time spent sedentary). Quality of life was significantly higher and walking limitation was lower in the sufficiently active and ≥10 h/day sedentary group compared to the reference group. Balance confidence was significantly reduced among those in the insufficiently active and ≥10 h/day sedentary group. Generally, beta-coefficients were larger in those who were inactive and more sedentary compared to those who were inactive and less sedentary.

DISCUSSION

The aims of this study were to describe the patterns of self-reported physical activity and sedentary behaviour in people with MG and to explore associations between these health-related behaviours and self-reported fatigue, quality of life, walking limitation and balance confidence. The findings of this study indicate that despite over half of the participants being sufficiently active, over a quarter also spent ≥10 h/day sedentary. There were significant associations found between meeting physical activity guidelines and less fatigue, greater quality of life, less walking limitation and greater balance confidence, while no significant associations were found between these variables and sedentary behaviour alone. When patterns of physical activity and sedentary behaviour were combined, there were significant dose-response relationships between these behaviours. Larger beta-coefficients were noted in those who were inactive and more sedentary compared to those who were inactive and less sedentary, indicating that sedentary behaviour alone may have an important effect on these outcomes, particularly in those who are insufficiently physically active.

These findings follow a similar pattern to previous cross-sectional studies in people with MG where most participants were sufficiently active (100%, 78%, respectively) [28, 29] with minimal engagement in vigorous activity [18, 28–30]. Our findings on those attaining sufficient activity were lower (63%), as was the case in two other large studies where 52–54%[31] and 47%[8] of participants were considered sufficiently active. It is important to note these studies defined the threshold of sufficient physical activity differently (for example > 150 min/week or equivalent [28, 31] versus > 240 min/week [8], and so direct comparison is not possible. Two studies reported physical activity in steps/day and so the proportion of sufficiently active participants is unclear, however given 7–8,000 steps/day is congruent with sufficient activity levels [47], it can be inferred these samples had reasonable levels of physical activity based on median steps/day of 7,872 [18] and 8,801 [30].

Variability in findings could be for several reasons which complicates collective interpretation of these findings. Firstly, there is a potential recruitment bias in the studies that found higher physical activity [18, 28–30] as participants entered training interventions following activity monitoring as part of their baseline testing, potentially attracting participants particularly interested in physical activity. Secondly, inconsistency in measures used to collect this data is an important consideration and limits direct comparison of findings, given some of these studies used objective accelerometry [18, 28–30], others self-report measures [8], (as was done in our study) and one a combination [31]. Self-report measures generally underestimate sedentary time [48] and give mixed results in measuring physical activity when compared to device-based measures [49], further compromising capacity to draw direct comparisons between findings. Ultimately device-based measures are the most reliable tool [49], however, online self-report surveys facilitated larger samples sizes in our study and the other studies using this method [8, 31] compared to those using device-based measures [28, 29]. This is important given the low global incidence of MG (0.3–2.8 per 100,000) [50]; online self-report allows for ease of distribution across larger geographical areas, enabling participation from people with MG who may not be located near where research is being conducted and subsequently increasing potential sample sizes. Furthermore, some studies only considered physical activity accrued in > 10 minute bouts [28, 31] and so physical activity of lesser duration was not captured, thereby potentially underestimating the total physical activity and impacting on whether participants were considered sufficiently or insufficiently active.

Physical activity is reported in the Active Australia Survey in > 10-minute bouts for walking, and any duration for moderate or vigorous activities. Thus, shorter durations of walking were not captured in our study. A previous study in MG found that only 30%of participants reached sufficient physical activity levels when calculating MVPA based on 10-minute bouts, however when any duration of MVPA was recorded all participants were considered sufficiently active [28]. It is possible our findings may underestimate total duration of physical activity and subsequently whether participants were sufficiently or insufficiently active for this reason. Recent evidence has found any duration of physical activity is beneficial [51], contradictory to previous public health guidelines that have suggested physical activity should be accumulated in 10-minute bouts [52]. This may be of particular relevance in this population, where accruing physical activity in shorter durations may be more feasible given the impairments associated with the disease.

High levels of sedentary time found in our study are similar to that of existing literature in people with MG [28–30]. Although no quantifiable guidelines exist to indicate target sedentary time, there is a dose-response relationship and risk of all-cause mortality gradually increases from 6–8 h/day, with a substantial increase noted from 9–9.5 h/day [22, 53]. This is concerning given people with MG have been reported to spend upwards of these thresholds in our study (9 h/day) and previous studies (11.5 h/day [28]; 10 h/day [30] and 10.9 h/day [31]). Investigation of the determinants of sedentary time in people with MG is warranted to develop targeted interventions to address this important determinant of health.

In this study, greater physical activity was significantly associated with favourable outcomes. This was similarly found in previous research in the case of fatigue and health-related quality of life [8]. However, this conflicts with other findings where no association was found between physical activity and health-related quality of life [28]. Co-variates may influence the findings of models.

Although there were no associations found be-tween sedentary behaviour alone and the outcomes assessed in this study, there were significant associations with these variables when patterns of sedentary behaviour were analysed in combination with sufficient versus insufficient physical activity. This is the first study to explore these associations in combination to single out the influence of sedentary behaviour. Our findings indicate that even in those who were inactive, lower levels of sedentary time (< 10 h/day) were associated with less fatigue, higher quality of life and less walking limitation compared to those with higher sedentary time (≥10 h/day). This is a promising finding, potentially suggesting that sedentary behaviour may be an appropriate intervention target even when physical activity is low. Increased mortality risk associated with high sedentary time appears to be mitigated with increasing physical activity and even reversed in those who are in the highest quartile for physical activity (> 2130 METminutes.wk^–1) [27]. Considering the evidence indicating people with MG are generally sufficiently active however perform minimal vigorous activity, and are highly sedentary [28–30], further investigation is warranted into which health behaviour/s are best targeted in this population.

The findings of this study should be considered with respect to some limitations. The online self-report method of data collection impeded capacity to objectively measure disease severity, given there is no universally used self-report measure of disease severity in this population. Similarly, self-report relies on patients being well informed of their medical history and treatments to accurately report on these factors, particularly in the case of our study where we were unable to cross-check information with clinical files given the recruitment method. Subsequently, these potential confounding factors were not accounted for in our study. However, 87%of participants in our study were independently ambulant without an aid with a median MG-QoL-15 score of 14; which may indicate moderate disease severity [4]. The association between disease severity and physical activity in this population has been conflicting in prior studies and so this warrants further investigation [8, 29].

Overall, R² values of our models were generally low, indicating that there may be several other variables contributing to these relationships that warrant future investigation (including disease severity). For example, over half of the participants in our study reported at least one other comorbidity, which has had associations with these health behaviours in other studies in this population [8]. Future research investigating a greater number of potential contributing variables would be of benefit to improve understanding of these behaviours in people with MG.

The cross-sectional design gives insight into these behaviours at only one point in time and therefore limits the ability to determine direction of causality. Additionally, the online format gave participants the option to complete the survey any day of the week which although increases convenience, may have impacted reliability given the PAST measures sedentary time from the previous day only and sedentary time may differ between weekdays and weekend days [37].

The current study included an overrepresentation of females; given incidence of early-onset (< 50 years) MG is three times higher in females than males [54], this may explain the unequal representation given the relatively young age of our sample (48±15.5 years). Selection bias associated with web-based social media recruitment may have contributed to our young sample, given that older adults are typically underrepresented in web-based surveys [55]. Investigation into these behaviours across the lifespan is warranted to equitably capture people with MG of all ages.

In conclusion, although physical activity guidelines were met by over half of participants with MG in our study, participants also reported high levels of sedentary behaviour. Our findings provide preliminary evidence that free-living physical activity and sedentary behaviour may be potential intervention targets given our findings of associations between higher physical activity levels and lower sedentary time and less fatigue, higher quality of life, lower walking limitation and higher balance confidence. Further research is warranted to explore the impact of sedentary behaviour on MG-related symptoms, particularly in those who are physically inactive who may have challenges attaining enough physical activity to offset high sedentary time. There is a need for high quality, longitudinal studies with large sample sizes in individuals with MG that can further investigate and confirm the direction of the relationship between these variables.