Patients with Parkinson's disease (PD) commonly present with restrictive pulmonary dysfunction. Decreased respiratory muscle strength and endurance with increased dyspnea are observed in ~50–60% of patients with PD (1, 2), although their pulmonary disorders usually remain unnoticed until advanced stages of the disease (1–3). Previous studies have shown the effect of respiratory muscle training (RMT) on pulmonary function, swallowing function, and quality of life (4–6).

The autonomic nervous system is known to play a pivotal role in the regulation of lung ventilation, gas exchange, and smooth muscle function of the airway (7). Autonomic impairment is also an important non-motor feature of PD (8, 9). Furthermore, the observation that levodopa has limited effects on the improvement of pulmonary function in patients with PD may suggest that respiration is associated with motor function, which is mainly mediated by the dopaminergic system, and other networks (10–15). Breathing involves a complex reciprocal interaction of the respiratory neuron network (RNN) and the central autonomic network (CAN) (16), and these two networks interact harmoniously to maintain adequate respiratory function. Our previous study showed that there was a simultaneous improvement in pulmonary and cardiovascular autonomic function in patients with PD after RMT (17).

Although the short-term effect of RMT on pulmonary and autonomic functions has been demonstrated, there is a paucity of information on the durability of the training effect. In the current study, we monitored pulmonary and autonomic functions up to 18 months after the cessation of RMT in patients with PD and attempted to elucidate the detraining effect. These approaches to improve the long-term outcome and quality of life of patients with PD in clinical practice are promising.

To date, there is paucity of information on the detraining effect after RMT, although the treatment effects of RMT in patients with PD have been demonstrated in our previous study, as well as several previous reports (4–6, 17). The detraining effect after RMT on pulmonary function has been reported in a study conducted in patients with late-onset Pompe disease (LOPD) (26). Concerning the detraining effect on cardiovascular autonomic function after RMT, only a recent study was conducted in healthy older women (27). To the best of our knowledge, the current study is the first to address the detraining effect after RMT on pulmonary and cardiovascular autonomic functions in patients with PD for a longer period.

The improvements in pulmonary and cardiovascular autonomic functions decayed after the cessation of RMT. According to the current data, the former decay is slower than the latter. This seems reasonable because the effect of RMT on pulmonary function is direct, whereas the effect on cardiovascular autonomic function is indirect and less prominent. The improvement of pulmonary function, as indicated by MIP and MEP, remained significant until 6 months after the cessation of RMT (9 months after enrollment). The study by Jones et al. was performed in patients with LOPD and showed that the RMT effect was durable after 3 months of detraining (26). Their study did not have data for longer than 3 months of detraining. Regarding cardiovascular autonomic function, our data showed that the treatment effect lasted for less than 6 months. The effect lasted for much less than 6 months according to the study by Rodrigues et al., which revealed that the improvements in vagal function and heart rate variability induced by RMT were reversed by 4 weeks of detraining, although their study involved older healthy women (27).

Regarding the functional score, the H-Y stage was consistent throughout the study in both the RMT and control groups. The H-Y stage may not be sensitive enough to reflect the change in functional outcomes in these patients. There was significant improvement in UPDRS (subscores II, III, and total score) after RMT. All the patients enrolled in this study were on follow-up for more than 6 months, and their daily dose of anti-Parkinsonian agents was at a steady dosage. The antiparkinsonian medications were not changed during the 3 months of RMT. Thus, the improvement in UPDRS is likely due to RMT rather than medication change. The improvement in UPDRS (UPDRS subscore II, UPDRS subscore III, and UPDRS total score) between baseline and 6-month follow-up (3 months after RMT) did not show statistical difference among the three motor phenotypes (p = 0.127, p = 0.279, and p = 208, respectively. Repeated measure ANOVA). The improvement in UPDRS remained significant until 6 months after the cessation of RMT (9 months after enrollment) and was reversed by 18 months of detraining. The detraining curve of UPDRS was similar to that of pulmonary function, rather than cardiovascular autonomic function. This finding may be consistent with our findings because daily activity and motor function depend more on pulmonary function than on cardiovascular autonomic function. Autonomic impairment usually remains asymptomatic until advanced stages.

The main limitation of this study is that protocol adherence was not as good in the control group. Although our previous study allocated 37 patients to the control group (17), it led to a reduction in the number of cases in the control group during the follow-up. Only 20 patients in the control group completed the entire study. The most common reason for the inability of patients to continue with the protocol was worse daily function. The deterioration of daily function in those patients during the follow-up was so marked that they were unwilling to report to the hospital for the entire set of evaluations. Therefore, if those patients had been included for the assessments during the 9th and 21st months, the data of the control group would have become even worse. In contrast, 32 of the 38 patients in the RMT group completed the study protocol. Considering that the baseline conditions were similar in these two groups of patients, the functional deterioration was slower in the patients with RMT. In addition, some may argue that there were older age, more disease severity, and longer duration in the control group. Although the age, and disease severity and duration were not perfectly matched between control and study groups, we had done our best to do so, and the difference was not statistically significant.

This study demonstrated the detraining effect of RMT in patients with PD. The improvement in pulmonary function and functional outcomes may persist for at least 6 months after detraining. However, the effect on cardiovascular autonomic function was less than 6 months. Based on these findings, we recommend that RMT may be repeated at least 6 months after previous session for patients with PD to maintain optimal therapeutic effects.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of Chang Gung Medical Foundation (201702037B0D001). The patients/participants provided their written informed consent to participate in this study.

C-CH and C-HL conceptualized the study, developed the methodology, wrote, reviewed, and edited the manuscript. C-CH, Y-RL, F-AW, N-YK, B-CC, N-WT, and C-HL performed the formal analysis. Y-RL, F-AW, N-YK, B-CC, and N-WT conducted the investigation. C-HL provided the resources, supervised the study, was in charge of the project administration, and acquired the funding. C-CH wrote and prepared the original draft. All authors have read and agreed to the published version of the manuscript.

This study was supported by Grants from the Ministry of Science and Technology (MOST 106-2314-B-182A-072 and 107-2314-B-182A-046-MY2).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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