Interstitial lung disease progression in patients with anti-aminoacyl transfer-RNA-synthetase autoantibodies is characterized by higher levels of sCD163.

BACKGROUND: Patients with anti-tRNA autoantibodies are characterized by arthritis, mechanic´s hands, fever, Raynaud´s phenomenon, and interstitial lung disease (ILD), in at least two clinical scenarios: the antisynthetase syndrome (ASSD) and interstitial pneumonia with autoimmune features (IPAF). The anti-tRNA-ILD treatment is centered on the administration of corticosteroids and a wide variety of immunosuppressive drugs; however, the effectiveness of the treatment depends on factors not fully understood. This research work aimed to quantify the serum levels of two molecules related to pulmonary fibrosis and explore their relationship with the progression of ILD associated with ASSD METHODOLOGY: Serum levels of sCD163 and TGF-ß1 from baseline and after six months of treatment of ILD patients' positives to anti-tRNA were included in the current study. At six months, patients were classified as with or without ILD progression RESULTS: Forty patients were included (anti-Jo1, anti-PL7, anti-PL12, and anti-Ej). Five patients (12.5%) had ILD progression and were characterized by higher levels of sCD163 at baseline. Baseline sCD163 serum levels showed good discriminatory capacity in patients with ILD progression. On the other hand, at follow-up, serum TGF-ß1 levels significantly increased in both patients' groups, with and without progression CONCLUSION: Basal levels of sCD163 were higher in patients who later developed ILD progression and kinetics of both molecules suggests the participation of M2 macrophages in the development of ILD.

Evolution of Pulmonary Function in a Cohort of Patients with Interstitial Lung Disease and Positive for Antisynthetase Antibodies.

OBJECTIVE: To describe the evolution of the pulmonary function in patients with interstitial lung disease (ILD) who are positive for at least 1 of the antisynthetase antibodies (ASAB) after medical treatment, and to compare whether the evolution of pulmonary function is associated with the type of ASAB. METHODS: Patients with ILD and positive for at least 1 of the ASAB (anti-Jo1, anti-PL7, anti-PL12, anti-EJ, or anti-OJ) were included. The clinical evolution, time until death or censoring, and improvement of lung disease were registered. RESULTS: The study included 118 patients. Most of the patients had a high extent of ground glass opacities in high-resolution computed tomography (HRCT) and low extent of fibrosis. In the final evaluation of pulmonary function (median 749.5 days of followup), 67% of the patients had lung disease improvement. The improvement occurred within the first 6 months after initiating medical treatment; thereafter, pulmonary function remained stable in most of the patients. A decrease of the extent of ground glass opacities was demonstrated in HRCT at followup in those patients with pulmonary improvement. No differences were observed in the percentage of patients who achieved improvement between the ASAB groups, or in survival. CONCLUSION: Improvement of pulmonary function was observed in 67% of the patients. Improvement was observed in all ASAB groups and occurred within 6 months after initiating medical treatment.

An Open-label Study With Pirfenidone on Chronic Hypersensitivity Pneumonitis.

BACKGROUND: Chronic hypersensitivity pneumonitis (cHP) represents a severe lung disease often evolving to fibrosis with the subsequent destruction of the lung parenchyma. There are no approved therapies with confirmed efficacy to deal with this disease. METHODS: We performed an open-label, proof of concept study, to evaluate the efficacy and safety of pirfenidone added to immunosuppressive drugs on the treatment of cHP. We included 22 patients assigned to two groups: Group 1, nine patients that received prednisone plus azathioprine and Group 2, thirteen patients, received prednisone plus azathioprine and pirfenidone (ClinicalTrials.gov identifier NCT02496182). There were no significant imbalances in clinically relevant baseline characteristics between two study groups. RESULTS: After 1 year of treatment, inclusion of pirfenidone was not associated with improved forced vital capacity (primary end-point). A not significant tendency to show higher improvement of diffusion capacity of the lung for carbon monoxide (DLCO) was observed in the group receiving pirfenidone (p=0.06). Likewise, a significant improvement in the total score on the SGRQ was found in the group 2 (p=0.02) without differences in other two questionnaires related to quality of life (ATAQ-IPF and EQ-5D-3L). HRCT showed a decrease of the ground glass attenuation without changes in the fibrotic lesions and without differences between both groups. CONCLUSIONS: These findings suggest that the addition of pirfenidone to the anti-inflammatory treatment in patients with chronic HP may improve the outcome with acceptable safety profile. However, prospective randomized double-blind, placebo-controlled trials in largest cohorts are needed to validate its efficacy.