Pain problems were prevalent in the patients with ILD but only few studies were performed for this problem. It is the first time that study was performed to measure pain problems in the patients with ILD by SF-MPQ and a healthy control group, persons of similar age and gender without lung disease, were set in order to explore the characteristics of pain in the patients with ILD. In our present study, these findings indicate that pain was found commonly in both IPF and non-IPF ILDs, and the prevalence of this deficit was higher compared with the rates found in healthy controls. The main pain location in the patients with ILD was chest, joint and limb. The intensity of pain may be related to exposure history, 6MWD and mMRC score. Compared with the patients with ILD but without pain, patients with pain also experienced impaired physical and mental health status, which might be predominantly caused by more limitations in daily functions.
Significant pain is not considered as a typical characteristic of ILD. However, in some large cohort studies, higher prevalence of pain was found in ILD compared with that in the general population(28,29). It is in line with our findings that more than half patients with ILD suffered pain in their daily life, which is much higher than that in healthy controls. When it came to the other chronic diseases, pain is also mentioned frequently but most chronic diseases show more prevalent pain problems. A meta-analysis, including 1,571 articles were identified, reporting that pain prevalence of COPD in high-quality studies ranged from 32% to 60%, and comorbidity, nutritional status, QoL and several symptoms were related to pain (30). The prevalence of pain in patients with advanced CKD had been estimated at approximately 50%–70%(31). In 2018, a large healthy study in Norway (32), with 50,807 subjects, found that 43.0% in the diabetes group, and 75.4% in the arthritis group suffered from chronic pain, and a large European survey also reported arthritis was the most common cause of pain, followed by COPD and heart disease (29). More control groups with chronic diseases should be added in the future study to compared with the specifics of pain in ILD.
In the ILD individuals, the main pain locations were chest (46.2%) and joint (23.1%) among all the patients with ILD and pain. 57.1% of the patients with IPF and pain declared having chest pain, which was higher than non-IPF (40.0%). Kaisa’s study (8) also found that 31.2% (79/253) patients with IPF experienced chest pain. But a British study (33) about 111 patients with fibrotic ILD found that most frequently reported painful areas of these subjects were the back (34%) and lower limbs (25%), and they were similar compared with the patients with and without IPF. According to literatures about pulmonary disease, the causes of chest pain remain unclear which can be related to pulmonary loss of elasticity of the parietal pleura, pathological bronchial fibrosis, thoracic vertebral deformity, costotransverse, intervertebral arthropathy and activities related to breathing and postural dysfunction (34,35). The incidence of joint pain in patients with CTD-ILD was higher than in the patients with IPF in our study, which was in line with the previous studies (36). It was reported that the prevalence of joint pain in CTD-ILD patients could be explained by the high anti-cyclic citrullinated peptide antibody (anti-CCP) positivity in patients(37).
ILD Group experienced a higher pain intensity than HC Group both in feeling and emotion dimension. A higher intensity of pain in the patients with ILD was also associated with many factors in our study, including exposure history of ILD risk factors, longer distance of 6MWD (≥250m), higher mMRC score (2-4) and impaired SF-36 and HAD score. When undergoing severe dyspnea, the patients normally gave extra worse results of pulmonary function test, especially FVC, % predicted and DLCo, % predicted, and unsatisfied 6WMT, a practical and reliable measure of exercise tolerance that was widely used to assess the functional status of the patients with IPF(38), which showed the severity of the patients’ current conditions and reflect the current quality of life (39–41). It was reported in previous studies that the association between dyspnea severity in mMRC score and intensity of pain was reported in the previous studies(8,11), and the prevalence of chest pain in the patients with IPF had a positive linear relationship to increased mMRC score (8). In our study, compared with the patients with ILD but without pain, the ILDs with pain did have a higher mMRC score. Moreover, according to the results of MPQ, the pain intensity in the patients with ILD was greatly infected by dyspnea severity. But we didn’t see the relationship of pain intensity in the patients with ILD with the 6MWT SpO2 and FVC, % predicted, and DLCO, % predicted. Given that the patients with COPD showed obvious chronic pain and some patients with ILD also showed FEV1/FVC, % decline under 70% in the as the disease progress, we compared the intensity of pain in the patients with ILD, who were confirmed to experience pain problems but there were only negative results. Even the severity of dyspnea may have impacts on the intensity of pain (42), no apparent paradoxical relation between pain intensity of COPD and lung function (FEV1 and FEV1 percentage predicted) had been reported in previous pain studies on COPD (30,43–45). This inverse relationship, was also probably caused by selection bias, also could be interpreted that other symptoms like dyspnea were more distressing than pain, leading to more focuses on dyspnea and less on pain, also causing patients to be reluctant to spontaneously report pain(46–48).
The patients with ILD and pain suffered worse quality of life and psychological deficits, like symptoms of anxiety and depression(44), (45). The impaired HRQoL, according to results of SF-36, except for the poor total score, was mainly performed on mental health, bodily pain, vitality, and role emotional, which was reflected in the results of SF-MPQ and HADs. We further found that the pain intensity was related to the degree of depression and anxiety. In addition to increasing dyspnea, many of the ILDs, such as sarcoidosis and connective tissue disease ILDs, are associated with extrapulmonary manifestations that may also lead to pain and add tremendous burden on HRQoL and mental health.(49,50) Ryerson et. al. (10) reported the novel findings that baseline pain severity was associated with baseline depression score and particularly in the non-idiopathic pulmonary fibrosis population. Therefore, those indicated the need of healthcare providers, clinicians, and patients to pay greater attention to the patients with ILD and pain and consider strategies to minimize their impacts on the patients’ quality of life, healthcare utilization, and prognosis.
To our knowledge, this is the first study to investigate pain in patients with ILD, including the intensity, location, type and associated factors. However, generalizability beyond this specific group and setting is limited, as only 126 subjects from one hospital were included, there are some limits in our study results to a single time-point and does not allow us to describe the changes in pain or symptoms over time. Our study may be subjected to some selection bias and as some patients at a very advanced stage of the disease or close to death were likely to be lost from the cohort. Possibilities of false negative due to small sample size and false positive due to multiple testing. Another limitation is that the score of this questionnaire may be mixed with subjective feeling, especially the VAS score, and effected by individual verbal comprehension. The last but not the least, what was the accurate cause of pain in the patient with ILD couldn’t be completely sure in our study. In the future, a larger sample of cross- sectional or cohort studies may be conducted on factors related to pain intensity to further verify these results.