Physical Activity Influences Health-Related Quality of Life in Adults with Juvenile Idiopathic Arthritis

This cross-sectional study aimed to evaluate the impact of physical activity and physical fitness on the health-related quality of life (HQoL) of adult patients with Juvenile Idiopathic Arthritis (JIA). Fifty-nine JIA patients and sixty healthy individuals participated in this study. All individuals had the following evaluations performed: body composition (electrical bioimpedance), physical fitness (6 min walk test (6MWT)), physical activity level (International Physical Activity Questionnaire (IPAQ)), and HQoL (Quality of Life Questionnaire in relation to Health—Short Form (SF36)). Thirty-nine (66%) JIA patients were considered sedentary compared with 15 (25%) in the control group (p < 0.01). JIA patients had a lower HQoL compared with the control group in all variables studied (p < 0.05). JIA patients who were very physically active had better HQoL conditions in the categories of functional capacity (p = 0.001), limitations by physical aspects (p = 0.003), and emotional aspects (p = 0.002) compared with sedentary patients. JIA patients had more cardiovascular abnormalities and walked shorter distances compared with healthy controls in the 6MWT. In conclusion, we observed that HQoL was reduced in adults with JIA. A high percentage of JIA patients were sedentary with lower physical fitness, but physically active patients had a better HQoL than sedentary patients. The duration of physical activity, rather than intensity, influenced the mental aspects of HQoL.


Introduction
Juvenile Idiopathic Arthritis (JIA) is the most common rheumatic inflammatory disease in childhood and comprises a heterogeneous group of diseases characterized by arthritis of unknown origin with an onset before the age of 16 [1]. Although a proportion of patients have a favorable outcome, long-term follow-up has shown that approximately 50% of adults with JIA have persistent active disease and functional impairment (Steinbrocker classes III and IV) [2][3][4][5][6]. The frequency of disability varies according to JIA subtypes and the length of follow-up [2][3][4][5][6]. Despite treatment, functional disability progresses over time, leading to the need for joint replacement in a significant proportion of patients [6,7]. Disability related to extra-articular involvement, such as uveitis (which leads to glaucoma and reduced vision), is also a concern, and its occurrence has been observed in up to 30% of oligoarticular JIA [2][3][4][5][6]. Even in adults with JIA who were functionally independent (Steinbrocker I and II), significant limitations in daily living were observed, especially in mobility and physical activity [8].
This cross-sectional study took place between the years 2017 and 2019. The study was conducted in accordance with the Declaration of Helsinki, and this research was approved by the Research Ethics Committee of the State University of Campinas (UNICAMP) (CAAE = 65688017.8.0000.5404).

Participants
We invited consecutive JIA patients aged ≥18 who were followed at the outpatient pediatric rheumatology clinic at the University of Campinas (HC/UNICAMP). JIA was classified according to ILAR criteria [1]. We excluded JIA patients with active disease (Disease Activity Score in 28 Joints (DAS28) ≥ 2.6), patients with pain (visual analog scale (VAS) ≥ 3), and patients with functional impairment (Steinbrocker functional classification > 2) [29]. Fifty-nine JIA patients were included. Sixty healthy individuals with no history of chronic disease matched by sex, age, and sociocultural and economic background were included as controls. The control group consisted of friends and peers of JIA patients, who were invited when accompanying the patients to consults.

Body Composition
Body composition was analyzed using a vertical electrical bioimpedance scale model HBF-514C, brand OMRON ® (Bannockburn, Illinois). Initially, the equipment was configured by entering the data of height (meters), age (years), and sex. The subject was positioned on the scale barefoot, where he held a rod that was connected to the equipment at shoulder height. After finishing the reading, which took place in a few seconds, the device read the body weight, body mass index (BMI), percentage of body fat, total muscle mass, and estimated basal metabolic rate.

International Physical Activity Questionnaire (IPAQ)
The International Physical Activity Questionnaire (IPAQ) is a standardized instrument that was created to assess the physical activity level of any individual. It is an open questionnaire that analyzes the practice of physical activity in the last 7 days and can classify the individual into sedentary, irregularly active A and B, active, and very active [30,31] The Health-Related Quality of Life Questionnaire-Short Form (SF36) is a questionnaire that was developed to assess HQoL and allows the analysis of functional capacity, limitation by physical aspect, pain, general health status, vitality, aspects social, limitations due to emotional aspects, and the mental health of individuals. The SF36 still allows the separation of these mentioned elements, creating two distinct subgroups: a physical and a mental component [32].

Six-Minute Walk Test (6MWT)
The 6 min walk test (6MWT) is widely used to determine the physical fitness of individuals with low physical capacity and those who have some type of physical limitation. It is low-cost and easy to perform [33][34][35]. The participant aims to cover the greatest possible distance in a period of 6 min in the form of a walk. Blood pressure and heart rate values were measured before and after the test. We used the internal corridors of the HC/UNICAMP to carry out the test. The place was covered and ventilated, and two points were marked with a distance of 30 m between them. The performer was monitored for their perceived exertion. The individual could stop the activity at any time.

Statistical Analysis
The statistical analysis of this work was performed using IBM ® SPSS Statistics software version 20.0. Fisher's exact test was used to compare categorical variables. For normally distributed variables, we used Student's t-test. For non-parametric variables, we used the Mann-Whitney U-test. SF36 variables and IPAQ scores were compared with Pearson's correlation. The level of significance adopted for this research was p < 0.05. Post hoc power analysis was performed using the G*power program [36]. When analyzing the physical and mental components of the SF36 summary scores, we obtained effect sizes (d) of 1.75 and 1.37, respectively.

Results
We included 59 JIA patients (mean age 29.10 years, standard deviation (SD) = 9.18) and 60 healthy controls (median age = 30.41 ± 3.12 years). The JIA group had a mean disease duration of 18.85 ± 8. 83 years, with mean a DAS 28 score of 2.3 ± 0.98. The most frequently reported JIA subtypes were rheumatoid factor positive polyarticular (37.3%) and rheumatoid factor negative polyarticular (28.8%). Demographic information, diseaserelated features, and comorbidities are summarized in Table 1. Pharmacologic treatment was prescribed to 83% of JIA patients. Synthetic DMARDs (sDMARDs) were used by 62.7% of patients, 44% received biological DMARDs (bDMARDs), and 22% of JIA patients used prednisone with a mean dose of 13.85 ± 5.4 mg ( Table 1). Only 17% of JIA patients were not taking any DMARDs (Table 1).
The control group showed a greater height (169.43 ± 8.11 cm vs. 162.92 ± 9.33 cm; p < 0.001), body weight (69.15 ± 6.83 kg vs. 63.56 ± 15.37 kg; p = 0.037), and estimated basal metabolism (calories) (1700.25 ± 9.96 vs. 1421.34 ± 23.67; 0.039) compared with JIA patients. BMI, percentage of body fat, and total muscle mass did not differ significantly between groups (Table 2). Before the start of the 6MWT, JIA patients had significantly higher systolic blood pressure (SBP) (p < 0.001) and heart rate (HR) (p < 0.001) than controls (p < 0.001). The distance covered during the test was lower in the JIA group compared with healthy individuals (498 vs. 569 m; p= 0.015). After physical exertion, SBP (p = 0.015) and diastolic blood pressure (DBP) (p < 0.001) were higher in the JIA group than in the controls. We found no significant difference between the groups in the HR variable after physical exertion (Table 3). The weekly frequency of walking in the JIA group was lower than that in the control group (0.78 ± 1.43 vs. 2.48 ± 1.80; p < 0.001). We also observed a lower time dedicated to walking in JIA patients than in healthy individuals (Table 4). We did not find significant differences between the groups when comparing the weekly frequency of moderate-intensity physical activity (p = 0.132); however, the average time devoted to this practice was lower in individuals with JIA (p = 0.008). There were no significant statistical differences between the weekly frequency and duration of vigorous-intensity physical activity between the groups in this study ( Table 4).
The average time that the groups remained seated during the week was statistically similar. The mean time spent in the sitting position during the weekend was higher in JIA patients (15.14 ± 6.91 vs. 11.08 ± 3.14; p < 0.001) ( Table 4).
The number of individuals considered sedentary was higher in the JIA group than in the control group (66.1% vs. 25%; p < 0.001) ( Table 4).
The HQoL of JIA patients was significantly lower than that of healthy individuals ( Figure 1A). JIA patients who were very physically active had better HQoL conditions in the categories of functional capacity (p = 0.001), limitations by physical aspects (p = 0.003), and emotional aspects (p = 0.002) compared with those considered sedentary ( Figure 1B). In the control group, physical activity did not influence SF36 scores or subscores ( Figure 1C).   Both the frequency (p = 0.003; r = 0.071) and the weekly duration (p = 0.017; r = 0.029) of vigorous physical activity were positively correlated with the physical component of the SF36 (Table 5).

Discussion
Long-term follow-up of JIA patients has shown that a significant proportion of patients flare and have progressive disability, emphasizing the need for adult specialist care during the transition period [37][38][39]. HQoL is of concern in these patients since it influences study outcomes, work absenteeism, and social interactions [30][31][32][33][34][35][36][37]. Compared with age-and sex-matched adults, we observed a reduced HQoL in JIA patients, as previously reported [5,10,13,14]. Despite the exclusion from our study of variables previously associated with HQoL in JIA, such as active disease, pain, and physical disability, our cohort still had a worse HQoL compared with controls [5,13,25]. However, in our cohort, only 17% of JIA patients were off medication. The subjective burden of medication use is a known risk factor for worse HQoL in JIA, but we were not able to analyze this effect [5]. We did not observe differences in HQoL between JIA subtypes; however, the small sample size in each group could explain this difference in relation to previously reported results [37].
In our study, we observed that 66% of JIA patients were sedentary. A sedentary lifestyle, characterized by energy expenditure ≤ 1.5 metabolic equivalents (METs), is common in the general population and increases the risk of CVD [40,41]. Approximately 6% of CVD and 7% of type 2 diabetes mellitus (DM2) events are associated with sedentary behavior, directly influencing the financial costs directed toward health in developed countries [38]. In our study, we found that 20% of adult JIA patients had arterial hypertension and 14% had diabetes, a frequency significantly greater than that in healthy controls. During the course of the disease, JIA patients are exposed to inflammatory processes and medications, such as prednisone, that increase the risk of atherosclerosis, CVD, and mortality [42][43][44][45][46][47][48].
In our study, we observed that JIA patients had a lower cardiovascular capacity during the 6MWT test compared with their healthy peers. The 6MWT serves as a monitoring tool in clinical settings, especially for physical activity recommendations, and analyzes patients' functional capabilities over time [49,50]. We also observed that adult JIA patients walked a significantly shorter distance than healthy controls (498 vs. 570 m, p = 0.015), indicating low physical aerobic capacity, as previously reported [51,52]. Improving physical aerobic capacity is associated with CVD risk reduction [53,54]. We also observed that JIA patients spent more time in a sitting position during the weekend compared with controls (15 vs. 11 h; p < 0.001), increasingly consolidating the sedentary lifestyle of these individuals. A lack of physical activity reduces the anti-inflammatory response, compromises the cardiorespiratory and musculoskeletal systems, and increases disability [55,56]. Therefore, physical activity can help prevent joint stiffness and deformities, atrophy, and muscle contractures in patients with JIA, enhancing the functional capabilities of these individuals, increasing their longevity, and decreasing the risk of premature mortality [10][11][12][13][14].
In our study, we observed that only 25.4% of adult JIA patients were active or very active. JIA patients who were very physically active had a better HQoL compared with sedentary patients. Previous studies have shown that JIA patients have a low physical capacity, especially in activities of moderate and vigorous intensity [49,57]. The lack of opportunities and stimuli, the severity of the disease and joint pain, and fear are associated with less activity [19,50,58,59]. In addition, low aerobic and anaerobic capacity has been observed in JIA patients with a negative influence on their HQoL [6,16,17,23,50]. The influence of physical activity has mainly been studied in children and adolescents with JIA and has been studied less frequently in adults with JIA [5,11,12,60].
We observed that the physical domains of the SF36 were positively correlated with the duration of moderate activity and the weekly frequency and duration of vigorous activity. The mental component of the SF36 was correlated with walking duration, moderate activity, and the weekly frequency and duration of vigorous activity. These results suggest that to improve the mental aspects of HQoL, the duration of physical activity is more important than the intensity. In a previous study including children with JIA, Pilates was shown to improve both the mental and physical aspects of HQoL [69].
Our study has some limitations. We performed a single-center study and applied strict exclusion criteria in order to exclude pain and disability as risk factors; however, this reduced generalizability. Although we had adequate power, the sample size was small, and we were not able to analyze different JIA subcategories individually. We applied the IPAQ and did not have an objective method to assess physical activity. An intervention study analyzing the effect of an exercise program on HQoL will be our next step.
This study suggests important clinical implications. A high percentage of our adult JIA patients had sedentary behavior, and they had hypertension and diabetes more frequently than the control group. These are relevant CVD risk factors that physicians should address in routine medical consults. Multidisciplinary healthcare team orientation would be of great value to these patients. In addition, we observed that the mental aspect of HQoL may be improved by duration, while the physical aspect was related to the intensity of physical activity.

Conclusions
In conclusion, sedentary behavior and reduced HQoL were more frequently observed in our adult JIA cohort than in controls. Physical activity was associated with a better HQoL. Thus, the practice of physical activity by these patients should be constantly encouraged by their families and multidisciplinary health teams as an effective part of their treatment plans.