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)

Hypersensitivity Pneumonitis: Diagnostic and Therapeutic Challenges.

Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases (ILD), that presents unique challenges for a confident diagnosis and limited therapeutic options. The disease is triggered by exposure to a wide variety of inciting antigens in susceptible individuals which results in T-cell hyperactivation and bronchioloalveolar inflammation. However, the genetic risk and the pathogenic mechanisms remain incompletely elucidated. Revised diagnostic criteria have recently been proposed, recommending to classify the disease in fibrotic and non-fibrotic HP which has strong therapeutic and outcome consequences. Confident diagnosis depends on the presence of clinical features of ILD, identification of the antigen(s), typical images on high-resolution computed tomography (HRCT), characteristic histopathological features, and lymphocytosis in the bronchoalveolar lavage. However, identifying the source of antigen is usually challenging, and HRCT and histopathology are often heterogeneous and not typical, supporting the notion that diagnosis should include a multidisciplinary assessment. Antigen removal and treating the inflammatory process is crucial in the progression of the disease since chronic persistent inflammation seems to be one of the mechanisms leading to lung fibrotic remodeling. Fibrotic HP has a few therapeutic options but evidence of efficacy is still scanty. Deciphering the molecular pathobiology of HP will contribute to open new therapeutic avenues and will provide vital insights in the search for novel diagnostic and prognostic biomarkers.

Lung involvement prevalence in patients with early rheumatoid arthritis without known pulmonary disease: a multicentric cross sectional study.

BACKGROUND: Clinically evident interstitial lung disease (ILD) affects between 10 and 42% of the patients with rheumatoid arthritis (RA). Airway involvement seems to be even more common. Most of the available evidence comes from studies performed in established RA patients. The aim of our study was to know the prevalence of non-diagnosed lung disease (airway and interstitial involvement) in patients with early RA and look for associated factors. METHODS: We designed an observational, multicenter, cross-sectional study, and included patients with RA of less than two years since diagnosis. We performed a structured questionnaire, HRCT and lung functional tests looking for lung disease, together with joint disease evaluation. We analyzed which variables were associated with the presence of lung disease on HRCT. RESULTS: We included 83 patients, 83% females. The median (IQR) of time since RA diagnosis was 3 (1-6) months. In the HRCT, 57 patients had airway compromisea (72%), and 6 had interstitial abnormalities (7.5%). The most common altertion found in lung functional tests was a reduced DLCO (14%). The presence of at least one abnormality in the physical exam was associated with lung involvement on HRCT [13 (21.6%) vs 0 (0%); p = 0.026]. Also, patients with lung involvement presented significantly lower values of FVC% and DLCO%, and higher values of RV/TLC. No variable related to joint involvement was found associated with alterations in HRCT. CONCLUSION: Our study shows that a large proportion of early RA patients has abnormal findings in HRCT. Further studies are required to confirm these findings.

Comorbidities of Patients With Idiopathic Pulmonary Fibrosis in Four Latin American Countries. Are There Differences by Country and Altitude?

Background: Comorbidities in idiopathic pulmonary fibrosis (IPF) affect quality of life, symptoms, disease progression and survival. It is unknown what are the comorbidities in patients with IPF in Latin America (LA) and if there are differences between countries. Our objective was to compare IPF comorbidities in four countries and analyze possible differences by altitude. Methods: Patients with IPF according 2012 ATS/ERS/JRS/ALAT guidelines, from two cities with an altitude of ≥2,250 m: Mexico City (Mexico) and Bogotá (Colombia) and from three at sea level: Buenos Aires (Argentina) and Lima and Trujillo (Peru). Comorbidities and pulmonary function tests were taken from clinical records. Possible pulmonary hypertension (PH) was defined by findings in the transthoracic echocardiogram of systolic pulmonary arterial pressure (sPAP) >36 mmHg or indirect signs of PH in the absence of other causes of PH. Emphysema as the concomitant finding of IPF criteria on chest tomography plus emphysema in the upper lobes. ANOVA or Kruskal Wallis and χ2-tests were used for comparison. Results: Two hundred and seventy-six patients were included, 50 from Argentina, 86 from Colombia, 91 from Mexico and 49 from Peru. There prevalence of PH was higher in Colombia and Mexico (p < 0.001), systemic arterial hypertension in Argentina (p < 0.015), gastro-esophageal reflux and dyslipidemia in Colombia and Argentina (p < 0.001) and diabetes mellitus in Mexico (p < 0.007). Other comorbidities were obesity (28.4%), coronary artery disease (15.2%) and emphysema (14.9%), with no differences between countries. There was more PH in the altitude cities than those at sea level (51.7 vs. 15.3%, p < 0.001). In patients from Bogotá and Mexico City, arterial oxygen pressure, saturation (p < 0.001) and carbon monoxide diffusing capacity (p = 0.004) were significantly lower than in cities at sea level. Conclusions: In this study with a significant number of patients, we were able to describe and compare the comorbidities of IPF in four LA countries, which contributes to the epidemiological data of this disease in the region. The main results were the differences in comorbidities between the countries and more PH in the subjects residing in the cities of higher altitude, a finding that should be validated in future studies.

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.

Lung involvement prevalence in patients with early rheumatoid arthritis without known pulmonary disease: a multicentric cross sectional study

Abstract Background: Clinically evident interstitial lung disease (ILD) affects between 10 and 42% of the patients with rheumatoid arthritis (RA). Airway involvement seems to be even more common. Most of the available evidence comes from studies performed in established RA patients. The aim of our study was to know the prevalence of non-diagnosed lung disease (airway and interstitial involvement) in patients with early RA and look for associated factors. Methods: We designed an observational, multicenter, cross-sectional study, and included patients with RA of less than two years since diagnosis. We performed a structured questionnaire, HRCT and lung functional tests looking for lung disease, together with joint disease evaluation. We analyzed which variables were associated with the presence of lung disease on HRCT. Results: We included 83 patients, 83% females. The median (IQR) of time since RA diagnosis was 3 (1-6) months. In the HRCT, 57 patients had airway compromisea (72%), and 6 had interstitial abnormalities (7.5%). The most common altertion found in lung functional tests was a reduced DLCO (14%). The presence of at least one abnormality in the physical exam was associated with lung involvement on HRCT [13 (21.6%) vs 0 (0%); p = 0.026]. Also, patients with lung involvement presented significantly lower values of FVC% and DLCO%, and higher values of RV/TLC. No variable related to joint involvement was found associated with alterations in HRCT. Conclusion: Our study shows that a large proportion of early RA patients has abnormal findings in HRCT. Further studies are required to confirm these findings.

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.

Rehabilitación respiratoria en pacientes con enfermedad pulmonar intersticial difusa. Experiencia de un hospital especializado de Argentina / Pulmonary Rehabilitation in Patients with Interstitial Lung Disease. Experience in a Specialized Hospital in Argentina

Introducción: Las enfermedades pulmonares intersticiales difusas generan en los pacientes intolerancia al ejercicio, disnea, y una disminución de la calidad de vida relacionada con la salud. La rehabilitación respiratoria tiene un rol importante en el cuidado estos pacientes. Materiales y Métodos: Se realizó un estudio retrospectivo en una cohorte de pacientes con enfermedad pulmonar intersticial difusa (EPID) sometida a rehabilitación respiratoria (RR) durante los años 2012 a 2015. Los pacientes realizaron 4 meses de RR, basado en entrenamiento aeróbico y fortalecimiento muscular de extremidades y tronco y educación en salud. Se estudió la calidad de vida con el cuestionario Saint George´s (SGRQ) y tolerancia al ejercicio (TE) con test de marcha de 6 minutos (TM6M) previo y posterior a RR. Se compararon los resultados entre pacientes con fibrosis pulmonar idiopática (FPI) y otras EPID. Resultados: Se incluyeron 93 pacientes (46 hombres), de los cuales 42 (44.09%) completaron el programa. Luego de la RR la media de puntaje del SGRQ disminuyo 8.7 puntos (IC 95%: 2.85-14.42), sin diferencia entre FPI y otros diagnósticos. La media de metros caminados en el TM6M mejoró 14.07 m sin alcanzar la significancia estadísticamente (p = 0.132). En el subgrupo de pacientes que caminó inicialmente menos de 400 m (n = 18), la mejoría fue clínica y estadísticamente significativa (40.8 m; p = 0.025). No encontramos diferencias en esta prueba en función del diagnóstico. Conclusiones: La RR en esta cohorte de pacientes con EPID demostró mejorar la calidad de vida y la tolerancia al ejercicio, sin diferencias en cuanto al diagnóstico específico.

Pulmonary Rehabilitation in Patients with Interstitial Lung Disease. Experience in a Specialized Hospital in Argentina / Rehabilitación respiratoria en pacientes con enfermedad pulmonar intersticial difusa. Experiencia de un hospital especializado de Argentina

Introduction: Interstitial lung diseases generate in patients exercise intolerance, dyspnea, and a decrease in health-related quality of life. Pulmonary Rehabilitation plays an important role in the treatment of these patients. Materials and Methods: We conducted a retrospective study in a cohort of patients with interstitial lung disease (DILD) who underwent Pulmonary Rehabilitation (PR) between 2012 and 2015. Patients completed a 4-month treatment program including aerobic, core, and upper and lower limbs strength training and health education. Quality of life was measured with the St. George´s Respiratory Questionnaire (SGRQ), and exercise tolerance with the 6-minute walk test (6MWT) pre- and post-PR. Results were compared among patients with idiopathic pulmonary fibrosis (IPF) and other ILDs. Results: 93 patients were included (46 male); 42 (44.09%) completed the program. After the PR, the SGRQ mean score decreased by 8.7 (95% CI [confidence interval]: 2.85-14.42), with no differences between the IPF and other diagnoses. The results of the 6MWT showed mean improvement of 14.07 m, not reaching statistical significance (p = 0.132). The subgroup of patients who walked less than 400 m (n = 18) showed clinical and statistically significant improvement (40.8 m; p = 0.025). We didn't find differences in this test in terms of diagnosis. Conclusions: PR in this cohort of patients with ILD showed improvement in quality of life and exercise tolerance, with no differences regarding the specific diagnosis.

Experiencia de la vida real con pirfenidona en la fibrosis pulmonar idiopática en Argentina. Estudio retrospectivo multicéntrico / Real-Life Experience with Pirfenidone in Idiopathic Pulmonary Fibrosis in Argentina. A Retrospective Multicenter Study

Introducción: La pirfenidona fue el primer fármaco antifibrótico aprobado en Argentina para fibrosis pulmonar idiopática. Los resultados de los ensayos clínicos podrían ser diferentes a los de la vida real. El objetivo primario fue estudiar la tolerancia de la pirfenidona en la vida real. El objetivo secundario analizar la eficacia y los motivos de suspensión. Materiales y métodos: Estudio observacional retrospectivo realizado en 4 centros especializados de Argentina. Se analizaron las historias clínicas de pacientes con fibrosis pulmonar idiopática que recibieron pirfenidona entre junio de 2013 y setiembre de 2016. Se analizaron efectos adversos y las variables que podrían influir en la ocurrencia de los mismos. Se comparó además la evolución de capacidad vital forzada (CVF%) entre los periodos prepirfenidona y pospirfenidona. Resultados: Cincuenta pacientes, 38 (76%) hombres, edad media (DE) 67,8 (8,36) años. La media (DE) de exposición a pirfenidona fue 645,68 (428,19) días, con una dosis diaria media (DE) de 2.064,56 mg (301,49). Se reportaron 19 eventos adversos en 15 pacientes (30%): náuseas (14%), astenia (10%) y rash cutáneo (8%). Dieciocho pacientes (36%) interrumpieron el tratamiento, uno definitivamente. El motivo más frecuente fue la falta de entrega de proovedores en 9 (18%). Comparamos la evolución de CVF% entre los períodos prepirfenidona y pospirfenidona, con una declinación media (DE) de CVF% de 4,03% (7,63) prepirfenidona y 2,64% (7,1) pospirfenidona, (p=0,534). Conclusiones: En nuestro estudio la pirfenidona fue bien tolerada y ha demostrado un enlentecimiento en la declinación de la CVF, aunque sin alcanzar significación estadística

Introduction: Pirfenidone was the first antifibrotic drug approved in Argentina for idiopathic pulmonary fibrosis (IPF). Outcomes in real life may differ from the results of clinical trials. The primary endpoint was to study the tolerance of pirfenidone in real life. Secondary endpoints were to analyze effectiveness and reasons for discontinuation. Materials and methods: Retrospective observational study conducted in 4 specialized centers in Argentina. We analyzed the medical records of patients with IPF who received pirfenidone between June 2013 and September 2016. Adverse events (AE) and the variables that could influence these results were analyzed. Forced vital capacity (FVC%) parameters were also compared between the pre-pirfenidone and post-pirfenidone periods. Results: Fifty patients were included, 38 (76%) men, with mean age (SD) 67.8 (8.36) years. Mean (SD) exposure to pirfenidone was 645.68 (428.19) days, with a mean daily dose (SD) of 2,064.56 mg (301.49). Nineteen AEs in 15 patients (30%) were reported: nausea (14%), asthenia (10%) and skin rash (8%). A total of 18 patients (36%) interrupted treatment, only 1 definitively. The most frequent reason for discontinuation was failure of suppliers to provide the drug (9 subjects; 18%). We compared the evolution of FVC% between the pre-pirfenidone and post-pirfenidone periods, and found a mean (SD) FVC% decline of 4.03% (7.63) pre-pirfenidone and 2.64% (7.1) post-pirfenidone (P=.534). Conclusions: In our study, pirfenidone was well tolerated and associated with a reduction in FVC decline, although without reaching statistical significance

Real-Life Experience with Pirfenidone in Idiopathic Pulmonary Fibrosis in Argentina. A Retrospective Multicenter Study. / Experiencia de la vida real con pirfenidona en la fibrosis pulmonar idiopática en Argentina. Estudio retrospectivo multicéntrico.

INTRODUCTION: Pirfenidone was the first antifibrotic drug approved in Argentina for idiopathic pulmonary fibrosis (IPF). Outcomes in real life may differ from the results of clinical trials. The primary endpoint was to study the tolerance of pirfenidone in real life. Secondary endpoints were to analyze effectiveness and reasons for discontinuation. MATERIALS AND METHODS: Retrospective observational study conducted in 4 specialized centers in Argentina. We analyzed the medical records of patients with IPF who received pirfenidone between June 2013 and September 2016. Adverse events (AE) and the variables that could influence these results were analyzed. Forced vital capacity (FVC%) parameters were also compared between the pre-pirfenidone and post-pirfenidone periods. RESULTS: Fifty patients were included, 38 (76%) men, with mean age (SD) 67.8 (8.36) years. Mean (SD) exposure to pirfenidone was 645.68 (428.19) days, with a mean daily dose (SD) of 2,064.56mg (301.49). Nineteen AEs in 15 patients (30%) were reported: nausea (14%), asthenia (10%) and skin rash (8%). A total of 18 patients (36%) interrupted treatment, only 1 definitively. The most frequent reason for discontinuation was failure of suppliers to provide the drug (9 subjects; 18%). We compared the evolution of FVC% between the pre-pirfenidone and post-pirfenidone periods, and found a mean (SD) FVC% decline of 4.03% (7.63) pre-pirfenidone and 2.64% (7.1) post-pirfenidone (P=.534). CONCLUSIONS: In our study, pirfenidone was well tolerated and associated with a reduction in FVC decline, although without reaching statistical significance.

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.

Enfermedad indiferenciada del tejido conectivo y enfermedad pulmonar intersticial: intentando definir patrones / Undifferentiated connective tissue disease and interstitial lung disease: trying to define patterns

Objetivos. Agrupar a los pacientes con enfermedad pulmonar intersticial (EPI) asociada a enfermedad indiferenciada del tejido conectivo (EITC) según la presencia o no de ciertas manifestaciones clínicas o inmunológicas, esperando encontrar diferentes expresiones tomográficas o funcionales. Métodos. Estudio de cohortes retrospectivas. Se incluyeron pacientes que cumplían criterios de Kinder para EITC. Se consideraron variables predictoras: manifestaciones «altamente específicas de enfermedad del tejido conectivo (ETC)» (Raynaud, xeroftalmia o artritis), títulos altos de anticuerpos antinucleares (ANA) (mayores a 1:320) y patrones específicos de ANA (centromérico, citoplásmico y nucleolar). El cambio en la capacidad vital forzada% (CVF%) en el tiempo y el patrón en TCAR fueron las variables de resultado estudiadas. Resultados. Se incluyeron 66 pacientes. Veintinueve presentaron al menos una manifestación «altamente específica de ETC» (43,94%), 16 ANA específico (28,57%) y 29 ANA alto título (43,94%). Aquellos con manifestaciones «altamente específicas de ETC» presentaron menor frecuencia de sexo masculino (10,34% vs 48,65%, p<0,001), menor edad en años (media 52 [DE14,58] vs 62,08 [9,46], p<0,001) y menor mediana de declinación de CVF% (1[RIC −1 a 10] vs −6 [RIC −16 a −4], p<0,006). En el análisis de regresión lineal múltiple la presencia de manifestaciones «altamente específicas de ETC» se asoció con mejoría en CVF% (coeficiente B de 13,25 [IC95% 2,41 a 24,09]). No encontramos asociaciones en cuanto al patrón en TACAR. Conclusiones. La presencia de manifestaciones «altamente específicas de ETC» se asoció con sexo femenino, menor edad al inicio y una evolución más favorable en cuanto a la CVF%, lo cual evidencia el impacto de las manifestaciones clínicas en la evolución de estos pacientes (AU)

Objectives. To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. Methods. Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: ‘highly specific’ connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and ‘specific’ ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. Results. Sixty-six patients were included. Twenty-nine (43.94%) showed at least one ‘highly specific’ CTD manifestation, 16 (28.57%) had a ‘specific’ ANA staining pattern and 29 (43.94%) high ANA titer. Patients with ‘highly specific’ CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [−1 to 10] vs -6% [−16 to −4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. Conclusion. The presence of ‘highly specific’ CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD (AU)

Traducción al español y validación del cuestionario Saint George específico para fibrosis pulmonar idiopática / Translation to Spanish and Validation of the Specific Saint George's Questionnaire for Idiopathic Pulmonary Fibrosis

Introducción: Las enfermedades pulmonares intersticiales (EPI) se asocian a una baja tolerancia al ejercicio, disnea y disminución de la calidad de vida relacionada con la salud (CVRS). La fibrosis pulmonar idiopática (FPI) es una de las más prevalentes del grupo. Para cuantificar su CVRS, se ha desarrollado una versión específica del cuestionario Saint George (SGRQ-I). Sin embargo, esta herramienta no está actualmente validada en el idioma español. El objetivo fue traducir al idioma español y validar el SGRQ-I en pacientes con FPI. Métodos: Se estudiaron la repetibilidad, la consistencia interna y la validez de constructo del SGRQ-I en español obtenido luego del proceso de traducción reversa. Resultados: Veintitrés pacientes con FPI completaron 2 veces el cuestionario traducido con 7 días de diferencia cada uno. Encontramos una buena concordancia en el test-retest, con un coeficiente de correlación intraclase (CCI) de 0,96 (p < 0,001). En el estudio de la consistencia interna hallamos un coeficiente alfa de Cronbach de 0,9 al incluir al valor total, y de 0,81 al excluirlo (p < 0,001), lo cual evidencia una buena interrelación de los diferentes ítems del cuestionario. El valor total del cuestionario mostro buena correlación con FVC% (r = -0,44; p = 0,033), DLCO% (r = -0,55; p = 0,011), PaO2 (r = -0,44; p = 0,036), disnea escala modificada de Medical Research Council (r = -0,65; p < 0,001), y pasos dados en 24 h (r = -0,47; p = 0,024). Conclusión: La versión en español del SGRQ-I desarrollada por nuestro grupo tiene buena consistencia interna, es reproducible y es válida para evaluar calidad de vida en pacientes con FPI (AU)

Introduction: Interstitial lung disease (ILD) is associated with low exercise tolerance, dyspnea, and decreased health-related quality of life (HRQL). Idiopathic pulmonary fibrosis (IPF) is one of the most prevalent in the group. A specific version of the Saint George's questionnaire (SGRQ-I) has been developed to quantify the HRQL of IPF patients. However, this tool is not currently validated in the Spanish language. The objective was to translate into Spanish and validate the specific Saint George's Respiratory Questionnaire for idiopathic pulmonary fibrosis (SGRQ-I). Methods: The repeatability, internal consistency and construct validity of the SGRQ-I in Spanish were analyzed after a backtranslation process. Results: In total, 23 outpatients with IPF completed the translated SGRQ-I twice, 7 days apart. Repeatability was studied, revealing good concordance in test-retest with an ICC (interclass correlation coefficient) of 0.96 (P < .001). Internal consistency was good for different questionnaire items (Cronbach's alpha of 0.9 including and 0.81 excluding the total value) (P<.001). The total score of the questionnaire showed good correlation with forced vital capacity FVC% (r = -0.44; P = .033), diffusing capacity of the lungs for carbon monoxide (DLCO%) (r = -0.55; P = .011), partial pressure of oxygen in arterial blood PaO2 (r=-0.44; P = .036), Medical Research Council Dyspnea scale (r=-0.65; P<.001), and number of steps taken in 24hours (r = -0.47; P =.024). Conclusions: The Spanish version of SGRQ-Ideveloped by our group shows good internal consistency, reproducibility and validity, so it can be used for the evaluation of quality of life (QOL) in IPF patients (AU)

Translation to Spanish and Validation of the Specific Saint George's Questionnaire for Idiopathic Pulmonary Fibrosis. / Traducción al español y validación del cuestionario Saint George específico para fibrosis pulmonar idiopática.

INTRODUCTION: Interstitial lung disease (ILD) is associated with low exercise tolerance, dyspnea, and decreased health-related quality of life (HRQL). Idiopathic pulmonary fibrosis (IPF) is one of the most prevalent in the group. A specific version of the Saint George's questionnaire (SGRQ-I) has been developed to quantify the HRQL of IPF patients. However, this tool is not currently validated in the Spanish language. The objective was to translate into Spanish and validate the specific Saint George's Respiratory Questionnaire for idiopathic pulmonary fibrosis (SGRQ-I). METHODS: The repeatability, internal consistency and construct validity of the SGRQ-I in Spanish were analyzed after a backtranslation process. RESULTS: In total, 23 outpatients with IPF completed the translated SGRQ-I twice, 7 days apart. Repeatability was studied, revealing good concordance in test-retest with an ICC (interclass correlation coefficient) of 0.96 (P<.001). Internal consistency was good for different questionnaire items (Cronbach's alpha of 0.9 including and 0.81 excluding the total value) (P<.001). The total score of the questionnaire showed good correlation with forced vital capacity FVC% (r=-0.44; P=.033), diffusing capacity of the lungs for carbon monoxide (DLCO%) (r=-0.55; P=.011), partial pressure of oxygen in arterial blood PaO2 (r=-0.44; P=.036), Medical Research Council Dyspnea scale (r=-0.65; P<.001), and number of steps taken in 24hours (r=-0.47; P=.024). CONCLUSIONS: The Spanish version of SGRQ-Ideveloped by our group shows good internal consistency, reproducibility and validity, so it can be used for the evaluation of quality of life (QOL) in IPF patients.

Undifferentiated connective tissue disease and interstitial lung disease: Trying to define patterns. / Enfermedad indiferenciada del tejido conectivo y enfermedad pulmonar intersticial: intentando definir patrones.

OBJECTIVES: To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. METHODS: Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: 'highly specific' connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and 'specific' ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. RESULTS: Sixty-six patients were included. Twenty-nine (43.94%) showed at least one 'highly specific' CTD manifestation, 16 (28.57%) had a 'specific' ANA staining pattern and 29 (43.94%) high ANA titer. Patients with 'highly specific' CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [-1 to 10] vs -6% [-16 to -4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. CONCLUSION: The presence of 'highly specific' CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD.