RA can manifest with various pulmonary complications, including ILD, pleural effusion, bronchiectasis, obliterative bronchiolitis, and pulmonary vascular disease. The prevalence of these manifestations varies depending on the specific type of pulmonary involvement and study population. ILD is recognized as a severe extra-articular complication of RA due to its high morbidity and mortality rates (25). The prevalence of RA-ILD varies across different studies. The present study reported a prevalence of 4.5%, which aligns with findings from previous studies conducted in Germany (2%) (26), the United States (9%) (9), Korea (2%) (4), and Malaysia (7%) (27). However, our study's prevalence rate is notably lower than the values reported in studies from China (15–43%) (11–13). The discrepancy in the prevalence reported by various studies may be attributed to variations in their screening and diagnostic methods employed. As with the various studies mentioned above, the present study used clinical data in combination with CXR as an initial step to determine the suspicion of ILD. The German population study employed multiple procedures, including CXR, PFT, HRCT, and bronchoalveolar lavage fluid analysis. On the other hand, the Chinese studies predominantly relied on HRCT as the primary screening tool. The higher prevalence observed in Chinese patients could be attributed to the greater sensitivity of HRCT as a diagnostic tool (11–13). Nevertheless, despite employing HRCT as a screening tool, the Malaysian investigation reported a relatively low prevalence of RA-ILD, as with our findings. The Malaysian study’s observation suggests that in addition to diagnostic methods, factors such as ethnicity, geography, and environmental influences may impact the development of ILD in RA. The role of routinely screening for ILD with HRCT in RA patients who have no respiratory symptoms and normal CXR is not clear. Several studies have demonstrated that many RA patients who had interstitial lung abnormalities on HRCT did not have clinical significance (28–30). Many studies and literature reviews suggest that HRCT should be obtained in RA patients who are suspected of having ILD, following an evaluation of their respiratory symptoms, CXR, and PFT (28–31). This approach appears to be appropriate in real-life practice, especially considering the relatively low prevalence of RA-ILD, as many patients have subclinical disease. However, once interstitial lung abnormalities are detected on HRCT, patients should undergo close monitoring. There is evidence suggesting that half of RA patients with interstitial lung abnormalities, even without respiratory symptoms, experience radiological progression in the next 1–2 years (32). Another significant factor influencing the high prevalence of RA-ILD in several studies is smoking, which has been strongly associated with RA-ILD (11, 13). One study reporting a prevalence of 25% for RA-ILD had a substantial proportion of smokers, who represented 20.7% of the population, compared to the present study in which smokers contributed only 7.6% (12).
Interestingly, the present study encountered a high rate of false-positive interpretations of CXR (45.8%) due to other lung pathological findings in our study population, such as bronchiectasis and obliterative bronchiolitis related to RA, as well as tuberculosis-related lesions. Additionally, two patients who were ultimately found to have no evidence of pulmonary disease on HRCT were initially reported as having ILD based on CXR findings. These false-positive chest X-ray interstitial opacities may have resulted from various factors, such as suboptimal patient positioning, overlapping anatomical structures, and normal anatomical variations. Employing lateral views in addition to posterior-anterior views for CXR may help mitigate the limitations associated with the latter.
The classification and identification of HRCT patterns in RA-ILD vary across studies, and several patterns have been described in the literature. The most commonly observed pattern in RA-ILD is the UIP pattern, with reported frequencies ranging from 40–62% of cases (33–35). The NSIP pattern ranks second most common (11–32% of cases) (34). Previous studies have indicated that the UIP pattern is more frequent in cases with a longer duration of RA. Interestingly, the present study and several other investigations involving patients with longstanding RA (over 5 years of disease duration) found NSIP to be the predominant ILD pattern in RA, with frequencies ranging from 29–59% of cases (11, 27, 36). The discrepancy in the most common pattern of ILD in RA among studies may be partly attributed to other risk factors for ILD including smoking. It has been reported that UIP is more common in smokers as compared with nonsmokers (37), whereas NSIP in RA is more common in nonsmokers (38). In this study, there was only one patient in RA-ILD was ever smoker leading to a lower proportion of UIP, when compared with other studies.
The most common spirometry finding in RA-ILD is a restrictive ventilatory defect. However, airflow obstruction may also coexist and can be observed in patients with bronchiectasis and bronchiolitis obliterans. In contrast, the present study reported that the majority of patients had normal spirometry results, which suggested less severe ILD in our cohort. Predictors for severe and progressive RA-ILD included smoking history, a UIP pattern, and a short duration of RA diagnosis (39–41). The explanation for the milder disease observed in the present study may be attributed to lower smoking history and a longer duration of RA diagnosis.
Consistent with previous studies, our findings indicate that older age is associated with a higher prevalence of ILD in patients with RA (11, 36). In line with the univariate analysis conducted in a study from Korea (4), our study revealed a significant association between poor functional status, indicated by high HAQ scores, and the presence of ILD. However, this association did not reach statistical significance in the subsequent multivariate analysis conducted in the Korean study. Our study did not perform a multivariate analysis due to the low number of RA-ILD patients. The present study did not identify significant associations between ILD and factors such as disease duration, disease activity, serology positivity, or smoking. This may be attributed to the unexpectedly small number of patients with RA-ILD included in our study, which could have limited our ability to detect such associations.
The present study was conducted in one of the largest tertiary hospitals in Thailand that specializes in managing RA-ILD patients. However, several limitations must be acknowledged. First, an unexpectedly small number of RA patients with ILD were included, potentially impacting the study's findings. Consequently, it was deemed inappropriate to perform multivariate analysis to identify independent factors associated with ILD in RA. Future research with a larger cohort is warranted to obtain more accurate results and identify comprehensive risk factors associated with ILD in this population. Second, CXR, which has low sensitivity for diagnosing ILD, was utilized as the screening tool. As a result, our study may have underestimated the true prevalence of RA-ILD. However, not all patients with RA undergo HRCT for screening ILD due to the low prevalence of RA-ILD, and many of them have subclinical disease as discussed above. Future research to investigate the utility of HRCT in screening for ILD in patients without respiratory symptoms and normal CXR is needed to assess its cost-effectiveness. Last, the present study lacks the longitudinal data to determine the clinical course and progression of RA-ILD and emphasizes the need for future research to address this issue in our population.