Avaliação dos métodos de rastreio da Doença Pulmonar Intersticial pré-clínica em pacientes com artrite reumatoide

Abstract

Introduction: Early diagnosis of interstitial lung disease related to rheumatoid arthritis (ILD-RA) remains a challenge in clinical practice. Current recommendations for screening patients with pre-clinical disease are based on evidence with low or very low certainty. Given this, the individualization of screening indications through measurable indicators remains an unmet need that deservers further investigation. Objectives: To evaluate the association between interstitial lung disease (ILD) screening methods, including serum Krebs von den Lungen-6 (KL6) levels, the 6-minute walk test (6MWT), and spirometry with lung volumes and carbon monoxide diffusion lung capacity (DLCO), with suggestive findings of pre-clinical ILD-RA on high-resolution chest computed tomography (HRCT). Methods: The study was conducted at the Hospital das Clínicas of the Federal University of Minas Gerais/Brazilian Hospital Service Company (HC/UFMG/EBSERH) between 2022 and 2023. Patients from the early arthritis and established RA clinics were included consecutively. All participants were previously diagnosed with RA, were respiratory asymptomatic, and had no prior diagnosis of ILD-RA. Clinical and sociodemographic data were collected and described. Patients underwent HRCT of the chest to identify ILD findings, including the presence of reticulation with or without ground-glass opacities, traction bronchiectasis, honeycombing, or isolated ground-glass opacities. Association and concurrent validity analyses were performed using Pearson correlation coefficient, biserial correlation test, and point-biserial correlation test. Cohen’s Kappa test was conducted to evaluate the agreement of categorical variables. Cut-off points for variables showing associations were calculated through receiver operating characteristic (ROC) curve construction. The study was approved by the HC/UFMG Ethics Committee, and all patients signed a written informed consent form. Results: Thirty-seven patients were included. The majority were female (86.5%), non-smokers (62.2%), and had high levels of autoantibodies (81%). The mean age of the sample was 54.4 years, with a median disease duration of 4.6 years. All HRCT findings were subtle, occupying less than 5% of lung volume, and no scan showed honeycombing. 29.7% of HRCTs were completely normal, while interstitial changes were found in 35% of them. One case (2.7%) presented overlap between suggestive ILD findings and airway changes. Other findings and airway changes accounted for 35.1% of cases. The 6MWT distance (6MWD) was associated with ILD findings on HRCT (rpb= 0.547; p= 0.001) and 462.55 meters was able to distinguish patients with suggestive ILD-RA findings on HRCT from those without such changes (AUC=0.813; 95% CI: 0.665 – 0.960; p= 0.003). Higher serum KL6 levels were also associated with ILD-RA findings on HRCT (rpb= 0.33; p=0.044) and were able to differentiate HRCTs with interstitial changes from normal HRCTs (p=0.046). However, KL6 did not differentiate interstitial changes from other changes (p=0.593), and its ROC curve did not reach statistical significance (p=0.61). Regarding spirometry, absolute DLCO values (rpb= 0.46; p=0.006), forced vital capacity (rpb= 0.43; p=0.008), and forced expiratory volume in the first second (rpb= 0.42; p=0.010) were also associated with ILD-RA findings on HRCT. Conclusion: A 6MWD of less than 462.55 meters and higher serum KL6 levels were associated with the presence of interstitial changes on HRCT in asymptomatic patients with RA from a respiratory perspective. Further studies with larger samples are needed to validate the findings of this study.