Interstitial lung disease in Sjögren’s disease: the portrait of a national cohort

Introduction: Apart from exocrine glands involvement with sicca symptoms, several extra-glandular manifestations can occur in Sjögren’s disease (SjD) such as pulmonary manifestations. Interstitial lung disease (ILD) is the most common lung manifestation in SjD. We aim to evaluate the presence of ILD in a national cohort of patients with SjD, identify variables associated with its development and progression, as well as describe the treatment used for SjD-ILD and its effectiveness and tolerability. Methods: We conducted an observational multicenter study of SjD-ILD patients prospectively followed in Reuma.pt. Demographic and clinical data were collected. We compared patient characteristics between groups using Chi-square or Fisher's exact test, Mann–Whitney or independent samples t-test, as appropriate. Logistic regression analysis was used to identify predictors of SjD- ILD. A linear mixed model with random intercept was used to compare results from pulmonary function tests (PFTs) before and after immunosuppression initiation. Results: Of the 1532 patients enrolled in the Reuma.pt-SjD protocol, 1333 (87%) had information on the presence of pulmonary manifestations. Among these, 127 (9.5%) had documented lung involvement, with ILD being the most common manifestation (74%). Ever smoking (OR=2.175; [95%CI:1.214-3.899]; p=0.009) and older age at SjD diagnosis (OR=1.047 per year; [95%CI:1.025-1.069]; p<0.001) were predictors of ILD. Nonspecific interstitial pneumonia was the most frequent ILD pattern (45.7%). Immunosuppression was used in 62 (66%) SjD-ILD patients and antifibrotics in eight patients (in seven of them in association with immunosuppression). Among the 26 patients with serial PFTs available, 10 (38.5%) showed ILD progression. Progressors had a higher forced vital capacity (FVC 96.8 ± 22.1 vs. 71.1 ± 21.4%; p=0.007) and diffusion capacity for carbon monoxide (DLCO 75.5 ± 12.1 vs. 50.2 ± 16.6%; p=0.002) at baseline and tend to have hypergammaglobulinemia more often (80% vs. 43.8%; p=0.069). Nevertheless, immunosuppression interrupted the decline of FVC (absolute value) and DLCO (percent predicted). Conclusion: This work demonstrated that a substantial proportion of SjD-ILD patients present with progressive fibrosis. Immunosuppression seems to delay the progression of lung disease. Therefore, identifying predictors for ILD development and progression is essential for recognizing which patients will require closer monitoring and intervention.