Calidad de vida en pacientes con esclerosis sistémica en confinamiento por pandemia de COVID-19 en Argentina / Quality of life in patients with systemic sclerosis in confinement due to the COVID-19 pandemic in Argentina

Introducción: los pacientes con enfermedades reumáticas tienen una calidad de vida significativamente deteriorada. La pandemia por COVID-19 tuvo un notable impacto sobre la población y los sistemas de salud de todo el mundo. Objetivos: en este trabajo nos proponemos conocer el impacto de la pandemia en la calidad de vida de los pacientes con esclerosis sistémica (ES) y cómo fue el acceso a la atención médica. Materiales y métodos: mediante encuestas anónimas y digitales a pacientes durante julio y agosto de 2020 se evaluó la calidad de vida utilizando el cuestionario de calidad de vida de la esclerosis sistémica (SScQoL). Además, se realizaron preguntas para evaluar el acceso al sistema de salud durante ese período. Resultados: se encuestaron 300 pacientes con ES. La mediana de afectación de la calidad de vida según el cuestionario utilizado fue de 17 (9,25-22) y el dolor fue el dominio más afectado. El 29,33% no hizo los controles médicos. El 74,33% refirió haber tenido estudios médicos pendientes al inicio de la cuarentena y solo el 25% pudo realizarlos. Conclusiones: los pacientes con ES presentaron compromiso de la calidad de vida durante la pandemia y mostraron dificultades en el acceso al sistema de salud.

Introduction: patients with rheumatic diseases have a significantly impaired quality of life. The COVID-19 pandemic has had a significant impact on the population and health systems around the world. Objectives: to analyze the impact of the pandemic on the quality of life and access to medical care of patients with systemic sclerosis (SS). Materials and methods: through anonymous and digital surveys of patients during July and August 2020, quality of life was assessed using the Systemic Sclerosis Quality of Life Questionnaire (SScQoL). In addition, questions were asked to assess access to the health system during that period. Results: 300 patients with SS were surveyed. The median quality of life affectation according to the questionnaire used was 17 (9.25-22), with pain being the most affected domain. Twenty-nine percent did not attend their medical appointments, 74.33% reported having pending medical studies at the beginning of the quarantine, and only 25% could carry them out. Conclusions: patients with SS presented compromised quality of life during the pandemic and showed difficulties in accessing the health system.

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.

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.

Occult primary Sjögren Syndrome in patients with interstitial pneumonia with autoimmune features.

INTRODUCTION/OBJECTIVES: To define the performance of Minor Salivary Gland Biopsy (MSGB) and Dry Eye Tests (DET) to detect occult Sjögren Syndrome (SS) among Interstitial Pneumonia with Autoimmune Features (IPAF) patients. METHODS: Prospective study. Interstitial Lung Disease (ILD) patients without defined Connective Tissue Disease and one or more IPAF classification domains or xerophthalmia were included. MSGB, Schirmer's test (ST) and Ocular Staining Score (OSS) were performed in a blinded manner by experienced specialists. MSGB with ≥1 focus of lymphocytes and Dry Eye Test (DET) with OSS ≥ 5 and/or ST < 5 s were considered positive. SS was diagnosed according to the ACR 2016 criteria. RESULTS: 534 patients on the first consult were screened. 67 patients had at least one IPAF criteria, 53 (79.1%) female, mean age (SD) 64.2 years old (10.8). Positive ST in 36 (53.7%), positive OSS in 29 (43.3%) and positive MSGB in 36 (53.7%) were found. Finally, 27 (40.3%) met SS diagnostic criteria. 25 (37.3%) and 18 (26.8%) of them did not report dry eyes or dry mouth, respectively. 53 (79.1%) had negative anti SSA/Ro, 57 (85.1%) had negative anti LA/SSB, 30 (44.7%) had negative ANA, and 52 (77.6%) had negative RF, respectively. A significantly higher proportion of ANA (+), anti-SSA/Ro (+), anti-SSB/La (+), positive DET and positive MSGB were found in the SS population. CONCLUSIONS: A significant proportion of patients with occult SS were found in our study. MSGB and DET may be considered in the evaluation of IPAF patients.

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.

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.

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.

Practical Approach to the Evaluation and Management of Rheumatoid Arthritis-Interstitial Lung Disease Based on its Proven and Hypothetical Mechanisms.

The prevalence of interstitial lung disease in patients with rheumatoid arthritis varies from 10 to 42%. Rheumatoid arthritis patients with interstitial lung disease have three times the risk of death compared with those without the disease. Prognosis seems to be related to the high-resolution computed tomography pattern. Usual interstitial pneumonia pattern, resembling idiopathic pulmonary fibrosis, carries a worse prognosis. Validated strategies to identify different phenotypes and assess the disease activity in rheumatoid arthritis interstitial lung disease are lacking. However, the utilization of high-resolution computed tomography, composed disease activity scores, and anti-citrullinated peptide antibodies titers can help to guide decisions in clinical practice. Mechanisms involved in lung disease may be different from those implicated in joint involvement. This could explain why in a significant proportion of cases, interstitial lung disease does not improve or even worsens with standard therapies used successfully to treat the joint component (e.g. anti- umor necrosis factor agents). In this scenario, a group of drugs that targets the adaptive immune response (e.g. rituximab or abatacept) seems to target more specifically the process that takes place in the lungs. Moreover, the recent emergence of anti-fibrotic drugs, which have already proven effective in idiopathic pulmonary fibrosis, may provide an alternative treatment strategy in rheumatoid arthritis-usual interstitial pneumonia. In this review, we propose a practical approach to the evaluation and therapy of rheumatoid arthritis interstitial lung disease. Validation of strategies directed to assess the activity of lung disease and identify the underlying mechanisms are needed. Clinical trials evaluating a therapeutic approach with specific targets based on the disease phenotype are warranted.

Dosaje de una glicoproteína rica en histidina en el lavado broncoalveolar de pacientes con enfermedades intersticiales difusas de pulmón / Dosage of Histidine Rich Glicoprotein in the Bronchoalveolar Lavage of Patients with Diffuse Interstitial Lung Disease

Introducción: La proteína rica en histidina (HRG) se encuentra en el plasma en altas concentraciones (100-150 μg/ml) y puede interaccionar con una gran variedad de moléculas. Se ha sugerido que esta proteína podría actuar como un reactante de fase aguda negativa, e incluso que podría participar en la proliferación de fibroblastos utilizando líneas celulares. Objetivo: Analizar los niveles de HRG en muestras de lavado broncoalveolar (LBA) de pacientes con enfermedad intersticial pulmonar difusa (EIPD) y evaluar su relación con la severidad de la enfermedad. Materiales y métodos: Se incluyeron muestras de 30 pacientes con EIPD y 17 sujetos control. Se dosaron los niveles de HRG en muestras de LBA por ELISA. Se recolectaron los datos función pulmonar. Resultados: Se encontró un aumento en la concentración de HRG en el LBA de pacientes con EIPD comparado con los sujetos control. Más aún, la concentración de HRG en el LBA fue inversamente proporcional a la capacidad vital forzada (CVF) de los pacientes (spearman r:-0.35; p < 0.05). Sin embargo, el análisis de cada subtipo de EIPD demostró que solo aquellos con fibrosis pulmonar idiopática (FPI) presentaron un incremento significativo respecto del grupo control (5.631.0 ± 303.7pg/ml vs 2.296.0 ± 349.4pg/ ml; p < 0.01). Conclusiones: Se describe por primera vez un aumento del nivel de HRG en pacientes con FPI, aunque nuevos estudios son requeridos para evaluar su rol como biomarcador asociado a la severidad o progresión de la enfermedad.

Introduction: The concentration of Histidine Rich Glycoprotein (HRG) in plasma is high (100-150 μg/ml). HRG interacts with a wide range of molecules. It has been suggested that this protein could act as a negative reactant acute protein and would be able to modulate fibroblast proliferation using cell lines. Objective: To analyze the levels of HRG in Bronchoalveolar Lavage (BAL) samples from patients with Interstitial Lung Diseases (ILD) and to evaluate its relationship with illness severity. Materials and Methods: Thirty patients with ILD and 17 control subjects were included. HRG was measured by ELISA. Pulmonary functions tests data were collected. Results: Increased levels of HRG in BAL samples from ILD patients were found compared with control subjects. Moreover, the levels of HRG showed an inverse correlation with the Forced Vital Capacity (FVC) values from patients with ILD (spearman r: -0.35; p < 0.05). However, when each subtype of ILD was analyzed, we observed that only patients with Idiopathic Pulmonary Fibrosis (IPF) showed a significant increase in levels of HRG compared with the control group (5.631,0 ± 303,7 pg/ml vs 2.296,0 ± 349,4 pg/ml; p < 0.01). Conclusions: This is the first time that increase of HRG levels from patients with IPF is described. Nevertheless, new studies are required to analyze its role as biomarker associated with severity or progression of the illness.

Citoquinas inflamatorias del lavado broncoalveolar en pacientes con enfermedades pulmonares intersticiales difusas: Utilidad en estudios de investigación / Inflammatory Cytokines in the Bronchoalveolar Lavage from Patients withDiffuse Interstitial Lung Diseases: Useful Research Studies

Las Enfermedades Pulmonares Intersticiales Difusas (EPID) se caracterizan por inflamación y fibrosis. El rol del lavado broncoalveolar (LBA) en el diagnóstico delas EPID, ha sido recientemente revalorizado. El objetivo de este trabajo fue evaluar los niveles de citoquinas inflamatorias del LBA asociado a las EPID. Recolectamos LBA de 28 pacientes con EPID y 15 sujetos con pulmones sanos. Realizamos el recuento total de células del LBA y determinamos los niveles de citoquinas por ELISA. Encontramos un incremento significativo en el número total de células y en los niveles de IL-6 en el LBA de los pacientes con Neumonía Intersticial no Específica (NINE), Neumonitis por Hipersensibilidad (NH) y Sarcoidosis en comparación con el grupo control. También, observamos un significativo incremento de IL-8 en el LBA de los pacientes con Fibrosis Pulmonar Idiopática /Neumonía Intersticial Usual (FPI/NIU) comparados con el grupo control. No encontramos relación entre los niveles de citoquinas y los parámetros de función pulmonar. El LBA podría jugar un importante rol para entender los procesos inflamatorios asociados a las EPID. Cuando el LBA es utilizado en conjunto con la información clínica completa, el recuento diferencial y el patrón inflamatorio; este podría contribuir con la evaluación diagnóstica. Sin embargo, el procesamiento del LBA y el análisis de este fluido son críticos para poder aprovechar dicha información. En este estudio, evaluamos la utilización del LBA como una herramienta para comprender los patrones inflamatorios asociados con las EPID.

Interstitial Lung Diseases (ILD) are characterized by inflammation and fibrosis. The role of bronchoalveolar lavage (BAL) in the diagnosis of ILD, has been recently revalued. The aim of this work was to evaluate BAL´s inflammatory cytokines associated with ILD. We collected BAL from 28 patients with ILD and15 control subjects with healthy lungs. We counted the whole BAL cell number and determined cytokines levels by ELISA. We found a significant increase in the whole BAL cell count and IL-6 levels in patients with fibrotic non-specific interstitial pneumonia (NSPI), hypersensitivity pneumonitis (HP) and sarcoidosis in comparison with the control group. We also observed a significant increase of IL-8 in BAL from usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) in comparison with the control group. We didn´t find relationship between cytokines levels and lung function parameters. BAL could play an important role to understand the inflammatory process associated with ILD. When BAL is used together with complete clinical information, BAL cell differential count and inflammatory patterns could contribute to the diagnostic evaluation. BAL processing and analysis of this fluid are critically important for providing useful information. In this study we evaluated the use of BAL as a research tool to understand inflammatory patterns associated with ILD.