To the best of our knowledge, this study is the first to comprehensively explore the levels and factors associated with QOL among patients with LOPD in China. Compared to previous research that compared Pompe patients with the healthy population, our study makes a significant contribution in that we took other rare disease patients as the comparison group. We believe that our choice of comparison group better highlights the problems faced by adult patients with LOPD, which are otherwise neglected by the existing health care and support systems in China. Another contribution of our study is that we focused on sub-dimensional scores rather than the total score of QOL, which can provide more specific suggestions for rare disease healthcare policymaking.
We found that adult patients with LOPD and non-Pompe rare disease patients in China had similar QOL in the domains of psychological and environmental health and social relationships; however, the former suffered an even lower QOL in the domain of physical health than the latter. This is, to some extent, consistent with previous findings in the literature where patients with PD were compared with the general population [8, 37, 38]. This is due to the fact that the special pathological features of PD, which cause the accumulation of glycogen in the skeletal muscles, heart, liver, and nervous system, may substantially restrain Pompe patients’ ability to move or breathe [37]. Our study notes that physical vulnerability features may influence patients with LOPD more than patients with other rare diseases. This finding calls for more efforts to promote physical-health-related QOL among people with LOPD. Since ERT has proven to be an important treatment for patients with PD, it is critical to enhance its affordability and accessibility in China. Meanwhile, as the study reveals, positive social interaction plays a very important role in increasing patients’ QOL across all domains. Hence, elevating the awareness of the public on PD, and encouraging them to get to know the patients with PD will mobilize more positive interactions between the patient community and the public. Moreover, effective community-based social support programs should also be conceived to create a more supportive social environment for patients with LOPD.
No statistical differences were observed in the domains of psychological health, environmental health, and social relationships of QOL. The impact of rare diseases on psychological, environmental, and social QOL may be more closely related to social misconceptions and even stigma of PD and RD patients than to the physiological nature of the diseases themselves [39]. Hence, regardless of the type of rare disease patients, their perceptions of psychological stress, a sense of security from the environment, and social interactions with others could be similar. Recent research has emphasized that psychological adjustments are beneficial to patients’ well-being [40]. More studies are needed to identify practical and effective ways for patients with LOPD and other rare diseases to improve their mental health.
Most patients with LOPD will not be cured in their lifetimes; hence, identifying ways to improve their QOL should be a core mission of patient-centered care. This study sought to contribute to this mission by exploring the contributors of patients’ QOL. Among all the potential contributors that we included in this study, gender did not seem to make a difference in terms of the four domains of QOL among the patients with LOPD in China. Age was negatively associated with the physical and environmental health domains of QOL, but it had no significant association with mental health or social relationships.
A systematic review among 1,214 rare disease patients in the United States noted that income level is positively associated with QOL in all domains [41]. Our study partly echoes these findings. On one hand, we found that employment is significantly correlated with patients’ psychological, environmental, and social relationship QOL. This is reasonable because employed patients tend to perform better in their social roles and have more chances to interact with other people. Meanwhile, higher levels of QOL may also allow patients to have a higher employment rate. On the other hand, the influences of employment on physical health were significant in univariate analysis but became non-significant in the multivariable model, implying a weak association between employment and patients’ physical health. Such a weak association may further suggest that physical condition may not be an obstacle for patients with LOPD to engage in work; rather, having a job may increase their subjective feelings of physical health. Therefore, policymakers and caregivers may need to think about how to create work opportunities that are suitable for these patients.
One surprising finding of our study is that there was no statistical difference between patients with LOPD and those with other rare diseases in terms of the proportion of patients suffering from CHE, even though ERT is recognized as one of the most expensive orphan drugs in the world. We think the most likely reason lies in the indicator of CHE itself. CHE is a binary indicator used for all populations and does not take into consideration disease-specific characteristics. Studies have indicated that rare diseases tend to pose a high economic burden on patients [42, 43]; in other words, the existing benchmark for judging CHE may be able to distinguish between rare and common diseases, but lacks sufficient sensitivity to distinguish between PD and other rare diseases. This inadequate sensitivity may also explain why nearly 70% of rare disease patients with and without PD both suffer from CHE, which is much higher than the average proportion of CHE among the general population (12.9%) [44].
The problem faced by patients with PD i.e., high healthcare expenditures, does not exist in China alone—in Europe, the average cost of ERT for PD is approximately EUR 300,000 (approximately RMB 2,360,000) per patient per year [1]. The financial burden of patients with PD in China can be even more devastating, because almost all patients with PD must pay out-of-pocket. There is almost no insurance coverage from the government or the market to help alleviate the burden.
Another noteworthy finding of our study was that CHE had no significant influence on the QOL in patients with LOPD compared with other non-PD rare disease patients, which is inconsistent with studies conducted in the United States and Europe [45, 46]. Although patients can have adverse infusion reactions, the expensive ERT has been highlighted in Western societies as a significant promoter of QOL, especially at the early stages of treatment [47]. Given the high price of ERT and the nearly complete lack of health insurance coverage on it in China at the time of this survey, a higher CHE may indicate the utilization of ERT or other forms of treatment, which should have potentially helped, at least, increase the patients’ physical health. However, this is not what we found in our study. Although no existing literature could provide explanation to such a fining, based our knowledge on the community of patients with LOPD in China, the majority of the patients who received ERT used the medicine neither continuously nor with sufficient doses. As a result, the effectiveness of the treatment was quite limited.
This study found that a higher level of reliance on assistive devices was negatively associated with all four dimensions of QOL. A large-scale study using the International Pompe Survey also revealed that wheelchair- and ventilator-dependent patients were more likely to report lower health-related QOL in terms of physical functioning, physical role functioning, and social functioning than the general population [8]. Yet in the same study, functional disability was not found to influence mental health-related QOL. However, our study found otherwise; that is, the influence of functional disability was pervasive on QOL in patients with LOPD. This may be because patients who rely heavily on assistive devices are less likely to go outdoors and have fewer chances to interact with others. More attention should be paid to these socially isolated patients. Future research should explore the impact of an active lifestyle, especially among patients who require assistive devices. The findings should be tested to determine whether they can be generalized to the global context.
Previous studies on QOL in patients with LOPD mostly focused on the financial and physical burdens presented by the disease; however, the humanistic aspect was largely overlooked. Dekker et al. indicated that the painful processes of learning, coping, and adapting to disease-related psychology could induce a humanistic burden on the social capital and social support of the patients and their caregivers [10]. Our findings indicated that promoting positive, successful interactions should be emphasized in improving QOL in patients with LOPD beyond the conventional emphasis on medication. Patient organizations may consider providing opportunities for patients to talk with their peers and share good news with friends in their programs. This study also found that unlike social interaction, tangible emotional/informational and affectionate social support might not be associated with patients’ QOL. However, one review of the spiritual needs of chronic disease patients emphasized that the feeling of being in charge or being helpful is more effective in improving patients’ psychological resilience than the feeling of being weak or being helped [48]. Therefore, when promoting social interactions, QOL promotional programs and patient organizations may try to offer more opportunities for reciprocal interactions rather than treating the patients as recipients alone.
Limitations
There are a few limitations to this study. First, this is a self-response cross-sectional survey that involves a rather small sample size. The inference made from this sample needs to be carefully examined. Second, the data were collected by an online survey. Although this approach could maximize the coverage of patients residing sporadically over a large country, whether or not the subjects would be able to understand the questions correctly or to provide authentic answers are of concern. Third, we did not include other possible factors associated with LOPD or QOL, such as comorbidities, clinical symptoms, and accessibility to medical resources. Fourth, there is neither a specific QOL scale for rare disease patients nor for patients with LOPD in particular. Therefore, we used the WHOQOL-BREF, which consists of abstract questions that are not suitable for children. Hence, non-adult patients with LOPD or IOPD were excluded from our study. Further relevant studies are warranted.