Valor pronóstico de los niveles plasmáticos de IL13 en pacientes con artritis reumatoidea y enfermedad pulmonar intersticial: estudio de cohorte prospectiva / Prognostic value of IL13 plasmatic levels in patients with rheumatoid arthritis and interstitial lung disease: a prospective cohort study

Introducción: el objetivo de este estudio fue analizar la relación entre los valores de IL13 y su pronóstico en pacientes con artritis reumatoidea (AR) y enfermedad pulmonar intersticial (EPI). Materiales y métodos: estudio de cohorte prospectiva. Se midió IL13 en suero y se dividió la cohorte en dos grupos con la mediana de IL13 como punto de corte. Se estudió el tiempo hasta una caída de la capacidad vital forzada (CVF) mayor o igual al 5% con el método de Kaplan Meier (KM) y regresión de Cox. Resultados: se incluyeron 47 pacientes. La media (DE) de tiempo de seguimiento fue de 12,7 (12,5) meses. El estimador de KM a 15 meses fue de 0,48 (IC 95% 0,13-0,76) en el grupo con valores elevados de IL13 y de 0,86 (IC 95% 0,54-0,93) en el otro grupo (p=0,037). En el análisis de Cox multivariado los valores elevados de IL13 se asociaron con una caída de la CVF mayor o igual al 5% en el seguimiento (HR 17.64 (IC 95% 1,89-164,1) p=0,012). Conclusiones: los valores elevados de IL13 se asociaron con peor evolución funcional en esta cohorte prospectiva de pacientes con AR y EPI.

Introduction: the aim of our study was to analyze the relationship between the concentrations of IL13 in serum and the prognosis of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. Materials and methods: we conducted a prospective cohort study. We measured IL13 levels in serum. Patients were divided in two groups using the median of IL13 value as cut off point. Time to a decline of 5% or more in FVC% from basal measurement was estimated using Kaplan Meier method. Univariate and multivariate Cox models were applied. Results: we included 47 patients. The mean (SD) time of follow-up was 12.7 (12.5) months. The Kaplan Meier estimator at 15 months was 0.48 (CI 95% 0.13-0.76) in the group with higher values of IL13, and 0.86 (CI95% 0.54-0.93) in the other group (p=0.037). In the Cox multivariate analysis, the values of IL13 were significantly associated with a decline of 5% or more in FVC% in the follow-up (HR 17.64 (CI 95% 1.89-164.1) p=0.012). Conclusions: our results indicate that patients with higher values of IL13 in serum presented higher decline in FVC% during their follow-up.

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: ILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. METHODS: Multicentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. RESULTS: We included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. CONCLUSIONS: Worse baseline PF could be related to the absence of extra-thoracic symptoms and "classic" antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study / Enfermedad pulmonar intersticial asociada con miositis: Características clínicas y factores relacionados con la mejoría de la función pulmonar. Estudio latinoamericano multicéntrico de cohorte

Background and objectives: ILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. Methods: Multicentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. Results: We included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. Conclusions: Worse baseline PF could be related to the absence of extra-thoracic symptoms and “classic” antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.(AU)

Antecedentes y objetivos: Los pacientes con enfermedad pulmonar intersticial (EPI) pueden presentar positividad para autoanticuerpos específicos de enfermedades autoinmunes, como los anticuerpos mioespecíficos (AME) o mioasociados (AMA). Existe escasa información disponible sobre pronóstico y respuesta al tratamiento de estos pacientes. Nuestro objetivo fue describir las características clínicas, radiológicas, funcionales y pronósticas de una cohorte latinoamericana de pacientes con EPI y AME/AMA. Métodos: Estudio retrospectivo multicéntrico de una cohorte pacientes con EPI y AME/AMA, evaluados en tres centros latinoamericanos entre 2016 y 2018. Describimos variables clínicas, tomográficas y funcionales. Analizamos variables asociadas con valores funcionales bajos al inicio y mejoría funcional mediante regresión logística. Resultados: Incluimos 211 pacientes, 77,4% mujeres, con una media de edad de 57 años. Los anticuerpos más frecuentes fueron Ro-52 y Jo-1. Valores funcionales bajos al inicio se asociaron con la presencia de EPI desde el debut y con un patrón de neumonía intersticial no específica (NINE)/neumonía organizativa (NO) en la tomografía computarizada de alta resolución (TACAR). Se analizó la evolución funcional en 121 pacientes: 48% permanecieron estables y 33% presentaron mejoría. El patrón de NO en TACAR, se asoció significativamente con mejoría funcional, mientras que la presencia de EPI desde el debut y la ausencia de esclerodactilia mostraron una tendencia en el análisis multivariado. Conclusiones: Valores funcionales bajos al debut podrían asociarse con la ausencia de síntomas extratorácicos al inicio, por llevar a un diagnóstico y tratamiento tardíos. Por el contrario, la presencia de síntomas sistémicos al debut, junto con formas más agudas de EPI como NINE/NO podrían asociarse con mejoría funcional por permitir un diagnóstico y tratamiento precoz.(AU)

Ecografía pulmonar como predictor de terapia intensiva en neumonía por COVID-19 / Lung ultrasound as predictor of intensive therapy in COVID-19 pneumonia

Resumen La ecografía pulmonar (EP) ha demostrado ser una herramienta útil para detectar el grado de compromiso pulmonar en neumonía y síndrome de distrés respiratorio agudo. El presente estudio evalúa la asociación entre la puntuación de EP de 12 regiones y el ingreso de terapia intermedia a terapia intensiva en pacientes con neumonía por COVID-19. Se incluyó un total de 115 pacientes con diagnóstico de neumonía confirmada por radiografía de tórax, por SARS-CoV-2, se realizó una EP junto con la evaluación de laboratorio que incluyó la medición de marcadores inflamatorios (linfocitos, proteína C reactiva, Dímero D, procalcitonina, ferritina, lactato deshidrogenasa y pro péptido natriurético de tipo B). Se utilizó una puntuación ecográfica pul monar que caracteriza el grado de afección pulmonar como leve, moderado y grave, y se comparó el resultado con los marcadores inflamatorios de laboratorio. En el análisis univariado se observó una asociación entre la puntuación de la EP, los niveles elevados de procalcitonina y péptido natriurético cerebral y el ingreso a terapia intensiva. En el análisis multivariado solo la puntuación de EP fue un predictor independiente de requerimiento de terapia intensiva.

Abstract Lung ultrasound (LUS) has shown to be a useful tool to detect the degree of pulmonary involvement in patients with pneumonia and acute respiratory distress syndrome. The present study evaluates the association of the 12-region lung ultrasound score and the requirements of intensive care unit, in patients with COVID-19 infection who were admitted to intermediate care in a specialized hospital; 115 patients with a diagnosis of pneumonia confirmed by chest radiography secondary to SARS-CoV-2 were included, LUS was performed together with the laboratory evaluation that included the measurement of inflammatory biomarkers (lymphocytes, C-reactive protein, D-dimer, procalcitonin, ferritin, lactate dehydrogenase, and pro B-type natriuretic peptide). Lung ultrasound score was used, characterizing the degree of lung involvement as mild, moderate, and severe, and the results were compared with inflammatory biomarkers. In the univariate analysis, an association was observed between the lung ultrasound score, elevated levels of procalcitonin and brain natriuretic peptide, and the admission to intensive care. In the multivariate analysis, only the lung ultrasound score was an independent predictor of need for intensive therapy.

[Lung ultrasound as predictor of intensive therapy in COVID-19 pneumonia]. / Ecografía pulmonar como predictor de terapia intensiva en neumonía por COVID-19.

Lung ultrasound (LUS) has shown to be a useful tool to detect the degree of pulmonary involvement in patients with pneumonia and acute respiratory distress syndrome. The present study evaluates the association of the 12-region lung ultrasound score and the requirements of intensive care unit, in patients with COVID-19 infection who were admitted to intermediate care in a specialized hospital; 115 patients with a diagnosis of pneumonia confirmed by chest radiography secondary to SARS-CoV-2 were included, LUS was performed together with the laboratory evaluation that included the measurement of inflammatory biomarkers (lymphocytes, C-reactive protein, D-dimer, procalcitonin, ferritin, lactate dehydrogenase, and pro B-type natriuretic peptide). Lung ultrasound score was used, characterizing the degree of lung involvement as mild, moderate, and severe, and the results were compared with inflammatory biomarkers. In the univariate analysis, an association was observed between the lung ultrasound score, elevated levels of procalcitonin and brain natriuretic peptide, and the admission to intensive care. In the multivariate analysis, only the lung ultrasound score was an independent predictor of need for intensive therapy.

La ecografía pulmonar (EP) ha demostrado ser una herramienta útil para detectar el grado de compromiso pulmonar en neumonía y síndrome de distrés respiratorio agudo. El presente estudio evalúa la asociación entre la puntuación de EP de 12 regiones y el ingreso de terapia intermedia a terapia intensiva en pacientes con neumonía por COVID-19. Se incluyó un total de 115 pacientes con diagnóstico de neumonía confirmada por radiografía de tórax, por SARS-CoV-2, se realizó una EP junto con la evaluación de laboratorio que incluyó la medición de marcadores inflamatorios (linfocitos, proteína C reactiva, Dímero D, procalcitonina, ferritina, lactato deshidrogenasa y pro péptido natriurético de tipo B). Se utilizó una puntuación ecográfica pulmonar que caracteriza el grado de afección pulmonar como leve, moderado y grave, y se comparó el resultado con los marcadores inflamatorios de laboratorio. En el análisis univariado se observó una asociación entre la puntuación de la EP, los niveles elevados de procalcitonina y péptido natriurético cerebral y el ingreso a terapia intensiva. En el análisis multivariado solo la puntuación de EP fue un predictor independiente de requerimiento de terapia intensiva.

Development of a risk indicator score for the identification of interstitial lung disease in patients with rheumatoid arthritis / Desarrollo de una regla de predicción clínica para identificar enfermedad pulmonar intersticial en pacientes con artritis reumatoidea

Background: Clinically evident interstitial lung disease (ILD) affects 10%–42% of RA patients with prognostic implications. The aim of this study was to discern which factors are associated with the presence of ILD in RA patients and to develop a score that could help to stratify the risk of having ILD in RA patients. Methods: Case–control study. We included RA patients recruited from ILD and rheumatology clinics. We retrieved the following data: gender, age, presence of extra articular manifestations, disease activity scores, antibodies status, ESR, and medication use. Multivariate logistic regression was performed. A risk indicator score was developed. Results: Of 118 patients included in this study, 52 (44%) had RA-ILD (cases) and 66 (56%) had RA without ILD (controls). Twenty-six patients were male (22%), the mean age was 56.6±15.6 years. Five variables were significantly associated with the presence of ILD: male gender, smoking, extraarticular manifestations, a CDAI score>28, and ESR>80mm/h. The AUC of the final model curve was 0.86 (95%CI 0.79–0.92). Two potential cut-off points of the risk indicator score were chosen: a value of 2 points showed a sensitivity of 90.38% and a specificity of 63.64%, while a value of 4 points showed a sensitivity of 51.9% and a specificity of 90.9%. Conclusion: This study identified risk factors that could help identify which RA patients are at risk of having ILD through the development of a risk indicator score. This score needs to be validated in an independent cohort.(AU)

Introducción: La enfermedad pulmonar intersticial (EPI) clínicamente evidente afecta al 10-42% de los pacientes con Artritis Reumatoidea (AR), con impacto en el pronóstico. El objetivo de este estudio fue identificar factores asociados y desarrollar una regla para estratificar el riesgo de EPI en pacientes con AR. Métodos: Estudio de casos y controles. Se incluyeron pacientes con AR de una clínica de enfermedades intersticiales y un servicio de reumatología. Se consignaron datos demográficos, manifestaciones extraarticulares, scores de actividad de la enfermedad, autoanticuerpos, tratamiento. Se analizó con regresión logística multivariada. Resultados: Se incluyeron 118 pacientes con AR, 52 (44%) con EPI (casos) y 66 (56%) sin EPI (controles). Veintiséis (22%) hombres, media de edad 56±15.6 años. Cinco variables se asociaron significativamente con la presencia de EPI: género masculino, tabaquismo, manifestaciones extraarticulares, CDAI> 28, y eritrosedimentación> 80mm/h. El área bajo la curva del modelo final fue 0.86 (IC 95% 0.79-0.92). Se escogieron dos potenciales puntos de corte del score: 2 puntos con una sensibilidad del 90.38% y una especificidad del 63.64%, y 4 puntos con una sensibilidad del 51.9% y una especificidad del 90.9%. Conclusión: Nuestro estudio identificó variables que podrían ayudar a identificar que pacientes con AR se encuentran en riesgo de presentar EPI.(AU)

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: ILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. METHODS: Multicentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. RESULTS: We included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. CONCLUSIONS: Worse baseline PF could be related to the absence of extra-thoracic symptoms and "classic" antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.

Development of a risk indicator score for the identification of interstitial lung disease in patients with rheumatoid arthritis.

BACKGROUND: Clinically evident interstitial lung disease (ILD) affects 10%-42% of RA patients with prognostic implications. The aim of this study was to discern which factors are associated with the presence of ILD in RA patients and to develop a score that could help to stratify the risk of having ILD in RA patients. METHODS: Case-control study. We included RA patients recruited from ILD and rheumatology clinics. We retrieved the following data: gender, age, presence of extra articular manifestations, disease activity scores, antibodies status, ESR, and medication use. Multivariate logistic regression was performed. A risk indicator score was developed. RESULTS: Of 118 patients included in this study, 52 (44%) had RA-ILD (cases) and 66 (56%) had RA without ILD (controls). Twenty-six patients were male (22%), the mean age was 56.6±15.6 years. Five variables were significantly associated with the presence of ILD: male gender, smoking, extraarticular manifestations, a CDAI score>28, and ESR>80mm/h. The AUC of the final model curve was 0.86 (95%CI 0.79-0.92). Two potential cut-off points of the risk indicator score were chosen: a value of 2 points showed a sensitivity of 90.38% and a specificity of 63.64%, while a value of 4 points showed a sensitivity of 51.9% and a specificity of 90.9%. CONCLUSION: This study identified risk factors that could help identify which RA patients are at risk of having ILD through the development of a risk indicator score. This score needs to be validated in an independent cohort.

Comparative survival analysis between idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

INTRODUCTION: Chronic hypersensitivity pneumonitis (CHP) is an interstitial lung disease with limited treatment response and bad prognosis. Sometimes it is indistinguishable from idiopathic pulmonary fibrosis (IPF) becoming one of the main differential diagnosis. The aim of our study is to compare survival and functional decline between these two entities. METHODS: Survival and functional decline more than 10% in FVC were compared using Kaplan Meier (KM) method between patients with CHP and IPF. Cox proportional hazard analysis was used to identify independent predictors of survival and functional decline. RESULTS: 146 patients were included, 54 with CHP and 92 with IPF. KM rate for 2 years survival was 0.71 (CI 95% 0,6-0,8) for CHP group and 0,83 (CI 95% 0,66 - 0,92) for IPF (p=0,027). Nevertheless this difference disappeared using Cox proportional hazard analysis, the adjusted HR for survival among CHP patients was 0,53 (CI 95% 0,25-1,15) (p=0,11). There was no difference in functional evolution between the two groups. KM rate for a decline more than or equal to 10% was 0,64 for CHP (CI 95% 0,43-0,79) and 0,78 for IPF (IC 95% 0,6-0,88) (p=0,22). This observation did not change after using Cox proportional hazard analysis. CONCLUSIONS: Our study shows that both IPF and CHP are fibrosing interstitial diseases with a similar evolution and survival. It might be possible that therapeutic approach in patients with CHP should change in the light of these observations.

Correlation between Lung and Joint Involvement in Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Cross-Sectional Study.

BACKGROUND: Rheumatoid arthritis (RA) can affect the lungs in different manners, with interstitial lung disease (ILD) as the most serious manifestation. Although lung and joint compromise could be thought to evolve in parallel, there are data suggesting the opposite. In this study, we evaluated the relationship between lung and joint involvement in RA ILD. METHODS: An observational cross-sectional study of RA ILD patients evaluated from January 2015 to February 2017. Joint disease assessment included number of tender and swollen joints, patient's global assessment of disease activity, erythrocyte sedimentation rate (ESR) or C-reactive protein, and disease activity score (DAS28). Lung disease assessment included forced vital capacity, diffusion capacity (DLCO), and Goh high-resolution computed tomography (HRCT) score for total extent, ground glass, and reticular pattern. We studied the correlation between both components of the disease. RESULTS: We included 46 patients, 14 (30.4%) men, with a mean (SD) of the age of 59.9 years (11.89). 12 (26.09) patients were in remission or had low disease activity measured with DAS28. The HRCT showed usual interstitial pneumonia (UIP) pattern in 10 (21.7%), possible UIP in 18 (39.1%), and inconsistent with UIP in 18 (39.1%). We found a good correlation between the ESR and the ground glass score in the HRCT (r = 0.39; p = 0.03). However, we found no correlation between lung function tests or HRCT scores and the other components of the DAS28. CONCLUSIONS: We only found a good correlation between ESR and ground glass score. It is possible that different pathways of the immune response mediate damage in lungs and joints.