Benefits of Physical Training in Sarcoidosis

Sarcoidosis is a multisystem disorder of unknown cause(s) characterized by the formation of immune granulomas in involved organs, most often the lung and lymphatic system (but virtually any organ can be affected). The clinical presentation of sarcoidosis is highly variable: certain patients present acutely, with severe symptoms and/or multi-organ involvement; although some patients are entirely asymptomatic. Symptoms are generally nonspecific and include general weakness, arthralgias, reduced exercise capacity, dyspnea, and fatigue [1‐5]. In addition to the specific organ-related symptoms, these less specific disabling symptoms may have a major influence on the daily activities and the social and professional lives of the patients, resulting in a reduced quality of life (QOL) [6]. Distance covered during the six-minute walk test (6MWD) is often reduced and correlates with forced vital capacity (FVC) and fatigue severity [7, 8]. Fatigue may be explained by peripheral muscle weakness and exercise intolerance—each is influenced by multiple factors, including sarcoidosis-related skeletal muscle abnormalities, decreased pulmonary function, small fiber neuropathy, and deconditioning [9‐11].

In several chronic—including lung—diseases, physical training has been shown to improve exercise intolerance and peripheral muscle weakness [12, 13]. Limited data suggest that pulmonary rehabilitation—the backbone of which is an exercise program that most often includes a combination of aerobic and resistance training—or an exercise training program that runs outside the confines of a formal pulmonary rehabilitation program is a safe intervention [14‐17] that improves symptoms, physical functioning, and QoL in these patients [12, 14]. Recently, Marcellis and colleagues observed that in sarcoidosis patients, fatigue, physical functioning, and psychological health all improved in response to physical training [13]. Our group showed that a 12-week physical training program improved or maintained exercise capacity in patients with severe fibrotic sarcoidosis or progressive idiopathic pulmonary fibrosis [18].

The aim of this study was to examine whether a physical training program supervised by a physical therapist improves fatigue and exercise capacity in sarcoidosis patients.

Baseline characteristics for the 147 patients with evaluable data—including the 90 patients who returned at 3 months—are summarized in Table 1. Figure 1 displays the flow chart of the study.

At baseline, there were no between-group differences in demographic or clinical variables (e.g., pulmonary function tests, inflammatory markers, radiological findings, peripheral muscle strength or exercise capacity, or treatment (Tables 1, 2)). There were also no between-group differences with regard to fatigue and perceived exertion.

Concerning fatigue, we found an interaction effect of time with group (F = 6.27, p = 0.014). This indicates that while both groups started with the same level of fatigue, Group I showed a significantly larger decrease of fatigue compared with Group II (see Fig. 2). The change in fatigue was also found when looking at the cut-off scores. At baseline, the majority of patients were fatigued. At 3 months, FAS scores improved by 4 or more points (i.e., the minimal clinically important difference or MCID) in 74.4 % of the patients in Group I and 48.5% of patients in Group II (p = 0.032). Lung function tests did not change in either group (data not shown).

An interaction effect was also found with regard to the 6MWD % norm (F = 59.5, p < 0.001). The 6MWD % norm for Group I improved between baseline and 3 months, while the 6MWD remained the same in Group II. As shown in Fig. 3, similar results were found with regard to 6MWD distance (interaction effect: F = 72.2, p < 0.001).

Concerning EFMS, % predicted, no significant interaction effect (p = 0.129) was found. There is a significant increase across time in both groups (F = 9.25, p = 0.003) but no difference between the two groups (p = 0.907). For HGS % norm, no significant interaction effect (p = 0.933) was present, but we did find that the % decreased significantly across time (F = 446.5, p < 0.001) in both groups. No group difference was found.

With regard to the two types of Borg scores, the Modified Borg and the Borg RPE, no difference was found between the groups and across time.

We did find an interaction effect on the two SRT measures, SRT watts (F = 4.6, p = 0.034) and SRT VO₂ max, ml/kg/min (F = 6.3, p = 0.014), indicating different changes across time for both groups. Although the main effects for both measures showed that the difference between the groups was not significant.

In this study, we observed that a supervised, 12-week, aerobic exercise, and strength training program improves exercise performance, strength, and fatigue in patients with sarcoidosis. The results were independent of age, gender, time since diagnosis, baseline pulmonary function (and other markers of sarcoidosis severity), inflammatory status, or pharmacological interventions. Currently, a program like the one used at our center is not standard of care for patients with sarcoidosis, but we think it should be. The exercise program is similar to those used in pulmonary rehabilitation programs throughout the world; thus, most clinicians caring for sarcoidosis patients have access to this valuable adjunctive therapeutic modality. In fact, we would argue that pulmonary rehabilitation should be considered as a first-line therapy for patients suffering from sarcoidosis.

Patients with sarcoidosis are frequently limited by reduced exercise tolerance, muscle weakness, and impaired QOL [7, 32, 33]. Sarcoidosis imposes a burden on patient’s lives and fatigue is ubiquitous among sarcoidosis patients. Exercise programs and pulmonary rehabilitation are beneficial for patients with many respiratory diseases [12], and evidence on the benefits of pulmonary rehabilitation (PR) and exercise for sarcoidosis patients is increasing [13, 18, 34‐36]. Our study builds on the results of a study by Marcellis et al. who observed that fatigue declined and 6MWD and peripheral muscle strength improved after a 13-week physical training program in sarcoidosis patients [13]. Ryerson and his colleagues found that PR improved exercise capacity in interstitial lung disease (ILD) patients, regardless of baseline 6MWD, and patients with worse baseline functional capacity had greater improvements following PR [37]. This suggests that motivated patients with relatively severe functional impairment should still be offered PR (unless contraindications exist), because they stand to benefit most.

At baseline, we found strong—but far from perfect—correlations between SRT and both VO₂max and 6MWD. This suggests that the SRT (submaximal exercise test, cycling, not every-day activity in all patients) and 6MWD (submaximal exercise test, walking, every-day activity) assess different aspects of physical functioning. Regardless, the between-groups differences in both variables were significantly greater in the group completing the intervention. Because there is lack of clarity [38], future studies are needed to address the issue of which exercise modality (cycle ergometry, walking, or both) should be used to assess the effects of interventions aimed at improving physical functional capacity.

Sarcoidosis is a heterogeneous disease, making assessments of disease severity complex. For example, pulmonary function test may not reflect the severity of pulmonary sarcoidosis [39]; thus, incorporating metrics across a broad range of outcomes is needed to generate a comprehensive determination of sarcoidosis severity. This is likely best performed via a multidisciplinary approach [5] that incorporates the assessment of multiple domains of physical functioning—and because it is so common and intrusive—fatigue [7, 40]. Patients with any chronic illness are at risk for physical inactivity, which in turn can induce general deconditioning. Poor physical conditioning contributes to fatigue, dyspnea, and the vicious cycle of more physical inactivity [10, 15]. Our results suggest that physical therapy and exercise are capable of breaking this cycle. Given the complexity of sarcoidosis and the potential for multi-system involvement, the therapeutic approach to any one patient, including rehabilitation or physical exercise programs, should be comprehensive, well thought-out and tailored to his/her needs [34, 41‐44].

This study has several limitations. First, it was an observational study, lacking a randomized control group, and blinding was not possible. This could introduce bias. Patients who decided to complete the supervised training program were likely more motivated than the other patients to improve their physical performance. Finally, we did not assess the long-term effect of PR. Thus, it is unknown whether these benefits are sustained following a supervised trainings program and which patients experience the greatest benefits.

In conclusion, a supervised physical training program improves fatigue, exercise capacity, and peripheral muscle strength among sarcoidosis patients; these results were independent of age, gender, time since diagnosis, baseline pulmonary function (and other markers of sarcoidosis severity), inflammatory status, or pharmacological interventions. Physical training should be included in their management regimen. Further research is required to confirm which patients benefit most from exercise training (including the type offered in pulmonary rehabilitation programs), to determine which components of such a program are most valuable to patients with sarcoidosis and explore whether there are strategies that can be used to achieve long-term benefits.