Comparison of the role of clinical findings and laboratory markers in the differential diagnosis of connective tissue diseases in interstitial lung patients

Objective: The aim of this study was to compare the roles of clinical, laboratory, and radiological findings in the diagnostic process of connective tissue disease–associated interstitial lung disease (CTD-ILD), to characterize distinguishing features across patient subgroups, and to identify potential indicators that may contribute to earlier diagnosis. Materials and Methods: This single-center, prospective, cross-sectional observational study included 147 consecutive patients over 18 years of age who presented with a preliminary diagnosis of interstitial lung disease to the Departments of Pulmonology, Rheumatology, and Immunology at Karadeniz Technical University between 2023 and 2025, none of whom had a prior diagnosis of CTD-ILD. Demographic characteristics, respiratory and systemic symptoms, physical findings, autoantibody profiles, pulmonary function tests, six-minute walk test results, and thoracic CT findings were evaluated. CTD diagnoses were established based on clinical and serological criteria through multidisciplinary consultation. Data were analyzed using appropriate statistical methods. Results: The mean age of the patients was 64.6 ± 10.8 years, and 59.9% were women. Undifferentiated connective tissue disease was the most common CTD subtype. The most frequent respiratory symptoms were cough (65.3%) and exertional dyspnea (60.5%; velcro crackles 53.7%), while arthralgia/arthritis (72.1%) was the most prevalent clinical manifestation. Thoracic CT most commonly revealed reticulation and interlobular/interseptal thickening (78.2%), predominantly with basal distribution (51%). ANA positivity (75.5%) was the most frequent laboratory abnormality. Patients with a prior CTD diagnosis were often asymptomatic and exhibited significantly higher rates of RF, anti-CCP, anti-SSA/SSB positivity and joint involvement. In contrast, patients without a prior CTD diagnosis more frequently showed ANA, anti-SM/RNP, ACE, and total IgE positivity, suggesting possible subclinical autoimmunity. Among asymptomatic patients, RF and anti-CCP positivity were more common, whereas anti-Sm/RNP positivity was associated with symptomatic status. Several significant associations were found between clinical and laboratory findings, as well as between radiological and clinical findings; however, no v significant correlations were observed between laboratory markers and radiological patterns. RF and anti-CCP positivity were highest among patients with rheumatoid arthritis, ANA positivity predominated in the UCTD group, and anti-CENP-B was most frequent in systemic sclerosis. Conclusion: This study demonstrates that the diagnostic evaluation of CTDILD cannot rely solely on respiratory symptoms; instead, clinical findings, laboratory markers, autoantibody profiles, and radiological patterns must be assessed collectively. Autoantibodies such as RF, anti-CCP, ANA, and anti-SM/RNP may be associated with early or asymptomatic pulmonary involvement, indicating the need for closer monitoring of these patients. The significant correlation between radiological and clinical findings underscores the central role of thoracic CT in diagnosis. The findings highlight the need for multicenter and longitudinal studies to better define CTD-ILD phenotypes. Keywords: Connective tissue disease, interstitial lung disease, connective tissue disease–associated interstitial lung disease, autoantibodies