Determinants of physical activity level in children and adolescents with juvenile idiopathic arthritis.

Objective: One of the most frequently discussed physical parameters in juvenile idiopathic arthritis (JIA) is physical activity level. There is limited evidence about determinants of physical activity level in JIA. In this study, we aimed to investigate the determinants of physical activity level in children and adolescents with JIA. Materials and methods: Thirty-two JIA patients and 18 age- and sex-matched healthy individuals were included in the study. The age range was 8–18 years. Sociodemographic and clinical data of the participants were recorded. In both groups, anthropometry, fatigue, pain, knee extension muscle strength, gait variables, functional exercise capacity assessed by six-minute walk test (6MWT), and arterial stiffness were evaluated. Physical activity level was assessed by an accelerometer. Results: The disease activity level of the patients was low. Pain and fatigue scores were significantly higher in the JIA group compared to healthy controls (p < 0.05). Walking speed, physical activity level, time spent in low-intensity physical activity, time spent in moderate-to-vigorous-intensity physical activity, and 6MWT distance were significantly lower than in healthy controls (p < 0.05). Quadriceps muscle strength and arterial stiffness assessment results were similar in both groups (p > 0.05). In the JIA group, there was a positive correlation between physical activity and age, height, fat-free body mass, quadriceps muscle strength, and 6MWT distance (p < 0.05). Also, there was a negative correlation between physical activity and pain, fatigue, and cadence. Physical activity level was independently associated with 6MWT distance (42.9% of the variability). Conclusion: In mildly affected JIA patients, gait speed, functional exercise capacity, and physical activity level are affected. Functional exercise capacity is a determinant of physical activity level in JIA.

Zusammenfassung: Ziele: Einer der am häufigsten diskutierten körperlichen Parameter bei juveniler idiopathischer Arthritis (JIA) ist der körperliche Aktivitätsgrad. Es gibt begrenzte Evidenz für die Determinanten des körperlichen Aktivitätsgrads bei JIA. In der vorliegenden Studie war es das Ziel, die Determinanten des körperlichen Aktivitätsgrads bei Kindern und Jugendlichen mit JIA zu untersuchen. Material und Methoden: In die Studie wurden 32 JIA-Patienten und 18 gesunde Personen gleichen Alters und Geschlechts einbezogen. Die Altersspanne lag zwischen 8 und 18 Jahren. Soziodemografische und klinische Daten der Teilnehmer wurden dokumentiert. In beiden Gruppen wurden Anthropometrie, Erschöpfung, Schmerzen, Kniestreckungsmuskelkraft, Gangvariablen, funktionelle Übungskapazität durch 6‑min-Gehtest (6MWT) und arterielle Steifheit bewertet. Der körperliche Aktivitätsgrad wurde durch einen Beschleunigungsmesser beurteilt. Ergebnisse: Die Krankheitsaktivität der Patienten war gering. Die Werte für Schmerz und Erschöpfung waren in der JIA-Gruppe bedeutend höher als in der gesunden Kontrollgruppe (p < 0,05). Gehgeschwindigkeit, Ausmaß der körperlichen Aktivität; Zeit, die mit körperlicher Aktivität geringer Intensität verbracht wurde; Zeit, die mit körperlicher Aktivität mittlerer bis hoher Intensität verbracht wurde, und die Distanz im 6MWT waren bedeutend niedriger als bei den gesunden Kontrollpersonen (p < 0,05). Die Ergebnisse zur Bewertung der Quadrizeps-Muskelkraft und arteriellen Steifigkeit waren in den Gruppen ähnlich (p > 0,05). In der JIA-Gruppe gab es positive Korrelationen zwischen körperlicher Aktivität und Alter, Größe, fettfreiem Körpergewicht, Quadrizeps-Muskelkraft und 6MGT-Distanz (p < 0,05). Außerdem gab es negative Korrelationen zwischen körperlicher Aktivität, Schmerzen, Erschöpfung und Schrittfrequenz. Der körperliche Aktivitätsgrad war in unabhängiger Weise mit der 6MWT-Distanz assoziiert (42,9 % der Variabilität). Schlussfolgerung: Bei leicht betroffenen JIA-Patienten sind die Ganggeschwindigkeit, die funktionelle Belastbarkeit und der körperliche Aktivitätsgrad beeinträchtigt. Die funktionelle Trainingskapazität ist bei JIA ausschlaggebend für den körperlichen Aktivitätsgrad.

Keywords: Gait; Physical Activity; Muscle Strength; Functional Exercise Capacity; Juvenile idiopathic arthritis; Gang; Körperliche Aktivität; Muskelkraft; Funktionelle Übungskapazität; Juvenile idiopathische Arthritis

Scan QR code & read article online

Juvenile idiopathic arthritis (JIA) is an umbrella term that covers all arthritis forms of unknown origin beginning before the age of 16 and lasting longer than 6 weeks [[1]]. Recently, developments in medical therapy and the use of biological agents have improved the clinical profile in JIA and made it easier to focus on physical functions [[1]]. Previous studies have shown that the physical activity (PA) level is affected in JIA [[2]]. An increase in arterial stiffness has been demonstrated in children and adolescents with JIA [[4]]. The increase in arterial stiffness may be associated with physical inactivity, but this relationship has not been studied in childhood JIA patients.

Recent studies have evaluated the relationship between PA level and pain, fatigue, disease activity, and medication [[5]–[7]]. Submaximal exercise capacity and muscle strength are important physical fitness elements and associated with physical activity in healthy children [[8]]. Determining the predictors of physical activity and creating recommendations for these predictors can also make physical activity interventions more effective. There are limited numbers of studies in the literature examining the determinants of physical activity level. Previous studies have generally focused on clinical variables and symptoms as determinants of physical activity [[5], [9]]. Therefore, there is a need to investigate whether physical parameters are determinants of PA level.

We aimed to investigate the determinants of PA level in children and adolescents with JIA by focusing on physical functions. Thus, the objectives of this cross-sectional study were as follows:

• To compare body composition, pain, fatigue, muscle strength, gait parameters, PA level, functional exercise capacity, and arterial stiffness in patients with JIA and their healthy peers.
• To investigate which parameters, such as disease activity, pain, fatigue, arterial stiffness, knee extension strength, gait parameters, and functional exercise capacity, are determinants of PA level in patients with JIA.

We consecutively reviewed eligible patients with a planned routine visit at Dokuz Eylül University Hospital between August 2021 and February 2022. Forty JIA patients were invited to the study. While 32 of them agreed to participate in the study, 8 refused. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Dokuz Eylül University (2021/22–20). All participants and parents gave written informed consent.

For the control group, age- and sex-matched healthy individuals who applied to the pediatric rheumatology department of the Dokuz Eylül University Hospital and were not diagnosed with any chronic disease were invited to the study. The inclusion criteria for patients were i) diagnosis of JIA by a specialist pediatric rheumatologist according to the International League of Associations for Rheumatology (ILAR) criteria [[1]]; ii) age 8–18 years, iii) able to perform physical assessments and read. The inclusion criteria for controls were i) age 8–18 years; ii) able to perform physical assessments and read; iii) absence of diagnosed chronic or systemic disease.

The exclusion criteria for patients and healthy participants were i) serious kidney and liver involvement; ii) orthopedic or neurological problems that may interfere with testing; iii) infection; iv) mental disorders: v) surgery within the previous 6 months.

In a similar study in which predictors of knee extension strength were determined previously to consider the relationship between physical activity and knee extension [[10]], the smallest sample size was calculated using G*Power software (Version 3.1.9.2, Dusseldorf University, Dusseldorf, Germany). The sample size was determined as 32 based on the effect size of 1.17, the alpha error probability of 0.05, and the power of 95% as the study.

Age, gender, and family history (chronic diseases) were recorded. Body mass index (BMI) and lean body weight were evaluated using the Bodystat 1500 (Bodystat Ltd., Douglas, UK) device. The patients' disease duration, JIA subtype, drugs, and other comorbidities were retrieved from the hospital archive.

Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 71 (JADAS-71) [[11]]. Higher scores indicate higher disease activity.

Pain was evaluated with the visual analogue scale. Participants marked their pain level over the past week on a 10 cm line. Fatigue was assessed with a valid and reliable Turkish version of the Pediatric Quality of Life Inventory—Multidimensional Fatigue Scale (PedsQL-MFS) [[12]]. Higher scores on the scale indicate higher fatigue.

A hand-held dynamometer (Lafayette Manual Muscle Testing System; Lafayette Instrument Company, Lafayette, Indiana, USA) was used to measure the knee extension muscle strength of participants. The measurement was repeated three times and the best value was recorded in kilograms [[13]].

A wireless motion detection device and gait analysis software (G-Walk, BTS Bioengineering SpA, Italy) were used for gait analysis. The participant walked comfortably at a normal pace of their own choosing with a wireless motion detection device fixed with a waist belt at the L4‑5 level on an eight-meter track. Gait speed, cadence, stance phase and swing phase durations, right and left gait qualities were recorded [[14]].

The six-minute walk test (6MWT) was used to evaluate functional exercise capacity. The guideline of the American Thoracic Society was used for application of the test [[15]]. Heart rate was recorded before and after the test. Finally, the total distance walked by the participant was recorded in meters. Predicted 6MWT distance was calculated with a formula defined by Geiger et al. [[16]].

The ActiGraph wGT3X-BT model accelerometer (ActiGraph Inc., Pensacola, FL, USA) was used to measure the level and pattern of PA. Participants were instructed to wear the accelerometer for seven consecutive days on their non-dominant wrist during waking hours. After 7 days, the accelerometer's raw data were converted to mean counts per minute (cpm) by ActiLife 6 Software (ActiGraph Inc., Pensacola, FL, USA). We applied the cut-off points used by Bohr et al. [[3]]: light physical activity (LPA, cpm > 1500), moderate PA (MPA, cpm > 2000), and vigorous PA (VPA, cpm > 3000) [[17]].

Arterial stiffness was measured via a noninvasive method with the SphygmocorXCEL (AtCor Medical, Sydney, New South Wales, Australia) device, which measures automatically with a cuff. Augmentation index (ALX) and a pulse wave velocity (PWV) assessment were saved [[18]].

All statistical analyses were performed using the SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Normality of the distribution was checked using skewness–kurtosis tests and histograms. Continuous data were expressed as mean with standard deviation (SD) or median with 25th–75th percentile as appropriate, and categorical data as n (%). To assess differences between the groups, the independent-sample t‑test was used for parametric data, the Mann–Whitney U test for non-parametric data, and the chi-square test for categorical data. Correlations between the variables were investigated using the Pearson product-moment correlation coefficient or Spearman's rank-order correlation according to the normality of distribution. It was accepted that a correlation coefficient (r) between the variables of between 0.20 and 0.39 is a weak correlation, of between 0.40 and 0.59 is moderate, of between 0.60 and 0.79 is strong, and of between 0.80 and 1.0 is a very strong correlation [[19]]. Multiple linear regression analysis with the enter model was performed to find the independent variables that had the greatest effect on physical activity level. P < 0.05 was considered statistically significant in all analyses.

A total of 32 patients followed up with the diagnosis of JIA and 18 healthy controls were included in our study. Of the JIA patients, 17 (53.1%) were girls and 15 (46.9%) were boys, and their mean age was 13.0 ± 2.8 (8–18) years. In the JIA group, there were 11 (34.5%) oligoarticular JIA (oJIA), 6 (18.8%) polyarticular JIA (pJIA), 8 (25%) enthesitis-related arthritis (ERA), 4 (12.5%) systemic-onset JIA (sJIA), and 3 (9.4%) psoriatic JIA (psJIA) as JIA subtypes. There was no significant difference between the JIA group and the control group in terms of age, gender, and anthropometric measures (Table 1). There was a significant difference between the groups in terms of pain (p < 0.001) and fatigue (p < 0.05; Table 1). The JADAS-71 score in JIA patients was 3.9 ± 5.2, which was lower than the value of 4.2 stated by Consolara et al. [[20]]. Thus, the disease activity level of JIA patients was low and their mean disease duration was 60.4 ± 48.6 months (2–181). 25% of the patients were not using drugs, 46.9% were on biologic agents, 40.6% were using disease-modifying antirheumatic drugs (DMARDs), and 9.4% were using nonsteroidal anti-inflammatory drugs (NSAIDs; Table 1).

Table 1 Participants' characteristics

Data were expressed mean ± standard deviation or median (interquartile range) BMI body mass index, PedsQL-MFS Pediatric Quality of Life Inventory—Multidimensional Fatigue Scale, JADAS Juvenile Arthritis Disease Activity Score, JIA juvenile idiopathic arthritis, DMARDs disease-modifying antirheumatic drugs, NSAIDs nonsteroidal anti-inflammatory drugs a Independent-samples t-test b Pearson chi-square test c Mann–Whitney U test *Statistically significant p-value

In the JİA group, left knee extension mean muscle strength was 22.1 ± 6.7 kg, right knee extension mean muscle strength was 23.6 ± 7.2 kg, and there was no significant difference compared to healthy controls (Table 2).

Table 2 Physical functions and arterial stiffness results of participants

Data are expressed mean ± SD or median (IQR) 6MWT six-minute walk test, JIA juvenile idiopathic arthritis a Independent-samples t-test b Mann–Whitney U test *Statistically significant p-value

The mean 6MWT distance of JIA patients was 585.1 ± 65.5 m and there was a significant difference between groups (p = 0.013). Distance walked in both groups was above 80% of the predicted value (Table 2). Max heart rate was also similar between groups (p = 0.07; Table 2).

The stance phase and swing phase were similar between the groups (p > 0.05). There was no difference between the groups in terms of gait quality for both lower extremities (p > 0.05). The mean gait speed in the JIA group was 1.1 ± 0.3 m/s and there was a significant difference between the groups (p = 0.041). In the JIA group, mean cadence was 111.0 ± 11.0 steps/min and there was no difference between groups (p = 0.086; Table 2).

In the JIA group, the median augmentation index was 14.5%, the mean pulse wave velocity was 4.7 ± 0.8 m/s, and there was no significant difference between the groups in terms of ALX (p = 0.413) and PWV (p = 0.337) values (Table 2).

The cpm measured by the accelerometer in the JIA and control groups were 458.3 ± 58.1 counts/min and 516.7 ± 60.5 counts/min, respectively. There was a significant difference between the groups in terms of cpm (p = 0.002) (Table 3). The median duration of light physical activity was 72.6 min, and the median moderate physical activity was 30.9 min in the JIA group; a significant difference was found between the groups in terms of light physical activity (p< 0.001) and moderate physical activity (p = 0.001; Table 3). The median vigorous physical activity in the JIA group was 5.7 min and there was no significant difference between the groups (p = 0.063; Table 3).

Table 3 Physical activity level and patterns of participants

Data were expressed mean ± standard deviation or median (interquartile range) cpm count per minute, LPA light physical activity, MPA moderate physical activity, VPA vigorous physical activity, JIA juvenile idiopathic arthritis a Independent samples t-test b Man–Whitney U test *Statistically significant p-value

According to the correlation analyses performed in the JIA group, there was a strong positive correlation between cpm and 6MWT distance (r = 0.7630, p < 0.001). A moderate correlation was found with height (r = 0.516, p = 0.002), age (r = 0.502, p = 0.003), lean body weight (r = 0.423, p = 0.016), and pain (r = −0.409, p = 0.02). In addition, a weak correlation was found between knee extension muscle strength (r = 0.374, p = 0.035) and general fatigue (r = −0.360, p = 0.043). There was a moderate negative correlation between cpm and cadence (r = −0.450, p = 0.010). There was no significant correlation between cpm and BMI, disease activity, disease duration, gait speed, ALX, and PWV (p > 0.05) (Table 4).

Table 4 Correlations of physical activity in patients with JIA

BMI body mass index, six-minute walk test, ALX augmentation Index, PWV pulse wave velocity, JIA juvenile idiopathic arthritis a Pearson correlation analysis b Spearman correlation analysis *p < 0.05

Age, height, lean body weight, left knee extension muscle strength, cadence, general fatigue, and 6MWT distance were considered in a multiple linear regression enter model. Functional exercise capacity, as measured by 6MWT, was found to be a determinant of physical activity, accounting for 42.9% of the variance (F = 4.505, p = 0.001; Table 5).

Table 5 Determinants of physical activity in patients with JIA

6MWT six-minute walk test, JIA juvenile idiopathic arthritis *p < 0.05, R = 0.655, R2 = 0.429 (F = 4.505, p = 0.001)

The main findings of this study showed that JIA patients with even mild involvement and low disease activity had more pain and fatigue, decreased gait speed, decreased physical activity level and moderate physical activity duration, and lower functional exercise capacity compared to their healthy peers. In addition, physical activity level was found to be associated with age, anthropometry, pain, fatigue, muscle strength, cadence, and exercise capacity. Functional exercise capacity was a predictor of physical activity level. In this study, we focused on evaluating the determinants of physical activity level together with physical outcome measures such as muscle strength, exercise capacity, and gait speed.

JIA patients in this study had low disease activity and were mildly affected according to the cut-off values specified in the Consolaro et al. study [[20]]. In accordance with other studies in the literature, we found that JIA patients had mild pain compared to their healthy peers [[21]]. Given the low disease activity, this may be related to the pain hypersensitization reported in the Cornelissen et al. study [[22]]. Also, in our study, more fatigue was reported in JIA patients than in their healthy peers.

Muscle atrophy and loss of muscle strength increase in accordance with the increase in inflammation in the active phase of the disease. Some studies reported that muscle strength decreases in JIA patients compared to their healthy peers [[10], [23]]. However, in our study, the muscle strength of JIA patients was found to be similar to their healthy peers. This may be related to early diagnosis and pharmacological intervention resulting in mild disease activity.

This study provides detailed results on functional exercise capacity in JIA patients. The 6MWT was submaximal in both groups according to heart rate after the test. In 6MWT, walking distance was more than 80% of the predicted value in both groups. Thus, we think our JIA patients were mildly affected. However, a significant difference was found between the groups in terms of both 6MWT distance and percent of predicted value. In previous studies, functional exercise capacity was found to be lower in JIA patients compared to their healthy peers. Impairment in functional exercise capacity is associated with symptoms such as pain and fatigue, decreased muscle strength, and decreased PA [[24]].

In our study, we found that gait speed was decreased in JIA patients with mild disease activity. According to a systematic review of gait in JIA disease, gait speed decreases in JIA patients and especially hip–knee joint kinematics is impaired [[26]]. However, we did not find any deterioration in parameters other than gait speed compared to healthy peers in our study. This may be related to the fact that early and intensive pharmacological intervention reduces gait disturbances, as reported by Hendry et al. [[27]].

Previous studies have interpreted arterial stiffness in JIA patients by looking at PWV. In our study, we found arterial stiffness to be similar between the groups. Some studies have found an increase in arterial stiffness relative to healthy peers [[4], [28]], but others have not found such a difference [[29]]. JIA subtype and disease activity level may play a role in finding different results in studies. It has been reported that arterial stiffness is higher in systemic-onset JIA and in patients with high disease activity [[4]].

Although there is no gold standard method for evaluating the level of PA in children, accelerometers provide very sensitive measurements [[31]]. In our study, we found that the PA level decreased in JIA patients compared to their healthy peers, and the duration of light physical activity and moderate physical activity decreased. However, their vigorous physical activity duration was similar to that of their healthy peers. Some previous studies that evaluated with accelerometry reported that the PA level and moderate-to-vigorous physical activity duration decreased in JIA patients [[3], [9], [32]]. However, Risum et al. reported that there is no decrease in cpm and moderate-to-vigorous physical activity in JIA patients compared to healthy peers [[33]]. In the study of Risum et al., the predominance of the female gender and the use of biological agents by the majority of the patients may be related to these results. Although the cpm data in our study were similar to those of other studies in the literature, the moderate-to-vigorous physical activity duration was 30.90 min and thus lower than in other studies [[3], [32]].

The PA level decrease in JIA raises the question of what the factors and determinants of PA might be. Previous studies have found that PA and age are negatively correlated [[5]]. However, we found a positive correlation in our study.

Results regarding the relationship between disease activity level and physical activity in JIA are conflicting [[9], [34]]. We did not find a relationship in our study. This may be the result of modern, early, and intensive pharmacotherapy. Similar to the literature, we found a negative correlation between PA and pain fatigue [[6]]. There is limited evidence regarding the relationship between PA and muscle strength in JIA. Risum et al. reported that muscle strength was associated with vigorous physical activity [[10]]. In this study, we explained the relationship between cpm and muscle strength. There is only one study in the literature examining PA and functional exercise capacity in JIA [[9]]. There is a high correlation between PA and functional exercise capacity. This is the first study to report the relationship between PA level and arterial stiffness in children with JIA. We found no relationship between PA and PWV. Future studies should evaluate PWV in patients with high disease activity and compare patients with low and high disease activity.

There are only three studies in the literature examining the determinants of PA and these studies generally focused on the clinical features of the disease [[6], [10], [16]]. Bos et al. found age, BMI, and functional disability to be predictors of PA level when they evaluated with the activity diary [[5]], while Risum et al. reported age and use of biological agents as predictors of PA level [[33]]. Nørgaard et al. found that disease activity level was not a clinical determinant of PA level [[9]]. We focused more on physical functions in our study and found functional exercise capacity to be clinical predictor of PA level. So, PA level is affected by functional exercise capacity, because PA contains submaximal efforts. Future studies should focus on the association between maximal exercise capacity and PA.

According to the results of this study, physical activity level decreases in children with low disease activity level who received early and effective treatment. One of the parameters that most affect the level of physical activity is the functional exercise capacity. Therefore, arrangements should be made to improve physical activity and functional exercise capacity in children and adolescents with JIA. Transportation during the day can be accomplished by bicycle or walking. More active games and activities such as dancing and walking should be planned rather than sedentary games and activities that require sitting. For leisure activities, hobbies that include physical activity should be offered to children and adolescents. Screen times should be shortened. It can be effective to track the number of steps and make it a fun race, especially through smartwatches, which have been widely used in recent years.

It is recommended for JIA patients to go trekking during good weather periods [[35]]. A club sport should definitely be offered to JIA patients. For children with JIA, individual or team sports, which are safer and without the risk of impact, may be preferred to contact sports activities. All these increases in physical activity can reduce chronic fatigue and improve physical function.

There were some limitations to our study. Firstly, we had difficulty recruiting more patients. Future studies may replicate these results with larger sample sizes. Secondly, future studies may examine PA according to JIA subgroups with larger sample sizes. PA may be affected due to several situations, which might be different in JIA subgroups. However, we did not aim to investigate this in our study. Also, the patients in our study had low disease activity. The same parameters should be examined repeatedly in children with different disease activities.

In summary, it was found that pain and fatigue were higher in individuals with JIA compared to healthy peers. Gait, PA, and functional exercise capacity were affected. Functional exercise capacity was found to be a determinant of PA level. In addition, because the patients with JIA included in our study had low disease activity level and low exposure, the same parameters should be examined repeatedly in children with different disease activity. Patients with well-controlled disease activity might be activated by the physical therapist to combat low physical functioning and fatigue. Daily exercise with incremental requirements, group exercises, membership in sports clubs, etc. might be recommended to the patients.

This work was supported by the Research Fund of the Dokuz Eylül University. Project number: 2021.KB.SAG.038. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

B.C. Ozdemir, S. Savci, A. Tanriverdi, B.O. Kahraman, R. Isguder, B. Makay, and E. Unsal declare that they have no competing interests.

All procedures performed in studies involving human participants or on human tissue were in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards.