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.

An Open-label Study With Pirfenidone on Chronic Hypersensitivity Pneumonitis / Estudio abierto con pirfenidona en neumonitis por hipersensibilidad crónica

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

ANTECEDENTES: La neumonitis por hipersensibilidad crónica es una enfermedad pulmonar grave que con frecuencia evoluciona hacia fibrosis, con la ulterior destrucción del parénquima pulmonar. No existen tratamientos aprobados con eficacia confirmada para el manejo de esta enfermedad. MÉTODOS: Llevamos a cabo un estudio preliminar de eficacia, abierto, para evaluar la eficacia y la seguridad de la pirfenidona sumada a los fármacos inmunosupresores en el tratamiento de la neumonitis por hipersensibilidad crónica. Se incluyeron 22 pacientes, que se asignaron a dos grupos: grupo 1, 9 pacientes que recibieron prednisona y azatioprina; y grupo 2, 13 pacientes que recibieron prednisona, azatioprina y pirfenidona (identificador NCT02496182 en ClinicalTrials.gov). No se observaron alteraciones significativas en las características clínicamente relevantes iniciales entre ambos grupos. RESULTADOS: Tras un año de tratamiento, la inclusión de la pirfenidona no se asoció con una mejora de la capacidad vital forzada (objetivo principal). Se observó una tendencia no significativa a mostrar una mayor mejora en la capacidad de difusión de monóxido de carbono (DLCO) por el pulmón en el grupo que recibió pirfenidona (p = 0,06). Asimismo, se encontró una mejora significativa en la puntuación total del cuestionario SGRQ en el grupo 2 (p = 0,02) sin encontrarse diferencias en los otros dos cuestionarios relacionados con la calidad de vida de los pacientes (ATAQ-IPF y EQ-5D-3L). La TAC de alta resolución mostró una disminución de la atenuación en «vidrio deslustrado», sin cambios en las fibrosis y sin diferencias entre ambos grupos. CONCLUSIONES: Estos hallazgos sugieren que añadir pirfenidona al tratamiento antiinflamatorio en pacientes con neumonitis por hipersensibilidad crónica podría mejorar el pronóstico con un perfil de seguridad aceptable. Sin embargo, se necesitan ensayos prospectivos aleatorizados doble ciego y controlados con placebo para validar esta eficacia

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.