Development of a physician-independent screening for rheumatoid arthritis-associated interstitial lung disease – a case-control and cohort study

Introduction: Interstitial lung disease (ILD) is a leading cause of death in rheumatoid arthritis (RA) patients. Given RA’s high prevalence, a physician-independent screening tool is needed. This study aimed to develop a patient-based, cost-effective questionnaire for RA-associated ILD (RA-ILD). Methods: A 26-item ILD symptom questionnaire was evaluated, adapted, and validated in two steps. Missing data were handled via multiple imputation. Step one involved item and principal component analyses in a multicenter cohort of ILD patients and healthy controls. Internal consistency was measured with McDonald’s omega, and score differences assessed with independent t-tests and Cohen’s d. Step two validated the questionnaire in monocentrically recruited ACPA- and RF-positive RA patients without prior pulmonary exams. RA-ILD was defined as abnormal lung ultrasound across 14 intercostal spaces with FVC or DLCO < 80% predicted. ROC, sensitivity, and specificity were calculated. Results: Step one included 174 ILD patients (46% female, mean age 62 ± 13, mean score 39 [95% CI 35–43]) and 67 controls (49% female, mean age 59 ± 12, mean score 8 [95% CI 4–12]). Internal consistency was excellent (ω = 0.93). Scores differed significantly (t = –11.71, p < 0.001, d = 1.36). Step two included 105 RA patients (76% female, mean age 59 ± 12, mean disease duration 9 ± 6 years, mean score 14 [95% CI 10–17]); 11 were suspected of RA-ILD (mean score 18 [95% CI 8–28]). A cut-off of 7.5 points yielded ROC 0.58, sensitivity 70.3%, specificity 47.7%, positive predictive value 13.6%, and negative predictive value 93.2%. Conclusion: The questionnaire demonstrated potential as a physician-independent, low-cost RA-ILD screening tool suitable for routine clinical use.