Bone marrow characterization in COPD: a multi-level network analysis.

BACKGROUND: Bone marrow (BM) produces hematopoietic and progenitor cells that contribute to distant organ inflammation and repair. Chronic obstructive pulmonary disease (COPD) is characterized by defective lung repair. Yet, BM composition has not been previously characterized in COPD patients. METHODS: In this prospective and controlled study, BM was obtained by sternum fine-needle aspiration in 35 COPD patients and 25 healthy controls (10 smokers and 15 never-smokers). BM cell count and immunophenotype were determined by microscopy and flow cytometry, respectively. Circulating inflammatory (C-reactive protein, IL-6, IL-8) and repair markers (HGF, IGF, TGF-ß, VEGF) were quantified by ELISA. Results were integrated by multi-level network correlation analysis. RESULTS: We found that: (1) there were no major significant pair wise differences between COPD patients and controls in the BM structural characteristics; (2) multi-level network analysis including patients and controls identifies a relation between immunity, repair and lung function not previously described, that remains in the COPD network but is absent in controls; and (3) this novel network identifies eosinophils as a potential mediator relating immunity and repair, particularly in patients with emphysema. CONCLUSIONS: Overall, these results suggest that BM is activated in COPD with impaired repair capacity in patients with more emphysema and/or higher circulating eosinophils.

Esputo inducido: una herramienta emergente en la caracterización celular y molecular de las enfermedades infamatorias de la vía aérea / Induced sputum: a tool emerging in the characterization cellular and molecular inflammatory diseases of the pathway aerial

El estudio de los investigadores Camargo y col publicado en RAMR en Junio de 2016 "Heterogeneidad en los fenotipos inflamatorios de los pacientes con EPOC: rol del recuento celular diferencial en esputo" enfoca un área de gran interés en esta etapa de búsqueda de biomarcadores que permiten reconocer subgrupos diferenciados de pacientes dentro de la heterogeneidad de las enfermedades inflamatorias crónicas de la vía aérea

Células mieloides supresoras: potencial vínculo entre la enfermedad pulmonar obstructiva crónica y el cáncer de pulmón / Myeloid-Derived Suppressor Cells: Possible Link Between Chronic Obstrucive Pulmonary Disease and Lung Cancer

La enfermedad pulmonar obstructiva crónica (EPOC) y el cáncer de pulmón (CP) son enfermedades prevalentes y representan causas principales de morbimortalidad a nivel global. Existe firme evidencia que demuestra que la EPOC es un factor de riesgo independiente de CP. La inflamación crónica juega un rol patogénico significativo en el desarrollo de las comorbilidades en la EPOC, y en particular en el CP. Diferentes mediadores inflamatorios celulares y moleculares promueven la tumorigénesis e inhiben la capacidad del sistema inmunitario de reconocer y eliminar células premalignas y malignas, proceso conocido como inmunovigilancia tumoral. Esta alteración de la inmunidad antitumoral se debe en parte a la expansión de las células mieloides supresoras (myeloid derived suppressor cells [MDSC]), que se caracterizan por suprimir la función efectora antitumoral de linfocitosT mediante la reducción de la expresión del T-cell receptor ζ (TCRζ) a través del catabolismo de la L-arginina. Los pacientes con EPOC y CP comparten un patrón similar de aumento y activación de las MDSC circulantes asociado a la reducción de la expresión del TCRζ y a la alteración de la función de los linfocitosT periféricos. Los objetivos de este artículo son revisar la evidencia sobre la asociación entre EPOC y CP, y analizar cómo la acumulación de MDSC podría alterar la inmunovigilancia tumoral en la EPOC y favorecer el desarrollo de CP

Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are prevalent diseases and are a leading cause of morbidity and mortality worldwide. There is strong evidence to show that COPD is an independent risk factor for LC. Chronic inflammation plays a significant pathogenic role in COPD comorbidities, particularly in LC. On the one hand, cellular and molecular inflammatory mediators promote carcinogenesis and, on the other, chronic inflammation impairs the capacity of the immune system to identify and destroy pre-malignant and malignant cells, a process known as tumor immune surveillance. This altered antitumor immunity is due in part to the expansion of myeloid-derived suppressor cells (MDSC), which are characterized by an ability to suppress the antitumor activity of T-cells by down-regulation of the T-cell receptor ζ chain (TCRζ) through the catabolism of L-arginine. COPD and LC patients share a common pattern of expansion and activation of circulating MDSC associated with TCRζ downregulation and impaired peripheral T-cell function. The objectives of this study were to review the evidence on the association between COPD and LC and to analyze how MDSC accumulation may alter tumor immune surveillance in COPD, and therefore, promote LC development

Myeloid-Derived Suppressor Cells: Possible Link Between Chronic Obstrucive Pulmonary Disease and Lung Cancer.

Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are prevalent diseases and are a leading cause of morbidity and mortality worldwide. There is strong evidence to show that COPD is an independent risk factor for LC. Chronic inflammation plays a significant pathogenic role in COPD comorbidities, particularly in LC. On the one hand, cellular and molecular inflammatory mediators promote carcinogenesis and, on the other, chronic inflammation impairs the capacity of the immune system to identify and destroy pre-malignant and malignant cells, a process known as tumor immune surveillance. This altered antitumor immunity is due in part to the expansion of myeloid-derived suppressor cells (MDSC), which are characterized by an ability to suppress the antitumor activity of T-cells by down-regulation of the T-cell receptor ζ chain (TCRζ) through the catabolism of L-arginine. COPD and LC patients share a common pattern of expansion and activation of circulating MDSC associated with TCRζ downregulation and impaired peripheral T-cell function. The objectives of this study were to review the evidence on the association between COPD and LC and to analyze how MDSC accumulation may alter tumor immune surveillance in COPD, and therefore, promote LC development.

Expansion of myeloid-derived suppressor cells in chronic obstructive pulmonary disease and lung cancer: potential link between inflammation and cancer.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer (LC). Myeloid-derived suppressor cells (MDSCs) down-regulate the T cell receptor ζ chain (TCR ζ) through L-arginine deprivation and lead to T cell dysfunction and deficient antitumor immunity. We hypothesized that abnormally high levels of MDSCs in COPD patients may alter tumor immunosurveillance. METHODS: We compared the proportion of circulating MDSCs (Lin-HLA-DR-/CD33+/CD11b+) (by flow cytometry), arginase I (ARG I) serum levels (by ELISA), and expression levels of TCR ζ on circulating lymphocytes (by flow cytometry) in 28 patients with LC, 62 subjects with COPD, 41 patients with both LC and COPD, 40 smokers with normal spirometry and 33 non-smoking controls. T cell proliferation assays were performed in a subgroup of participants (CFSE dilution protocol). RESULTS: We found that: (1) circulating MDSCs were up-regulated in COPD and LC patients (with and without COPD); (2) MDSCs expansion was associated with TCR ζ down-regulation in the three groups; (3) in LC patients, these findings were independent of COPD and tobacco smoking exposure; (4) TCR ζ down-regulation correlates with T cell hyporesponsiveness in COPD and LC patients. CONCLUSIONS: These results suggest that tumor immunosurveillance might be impaired in COPD and may contribute to the increased risk of LC reported in these patients.

Differential effects of smoking and COPD upon circulating myeloid derived suppressor cells.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by an enhanced and persistent innate and acquired immune response to tobacco smoking. Myeloid-derived suppressor cells (MDSCs) modulate T-cell responses by down-modulating the T cell receptor ζ chain (TCR ζ) through the catabolism of l-arginine. The effects of smoking on MDSCs and their potential participation in COPD immunopathogenesis have not been explored so far. METHODS: To investigate it, we compared the level of circulating Lineage-/HLA-DR-/CD33+/CD11b+ MDSCs, the serum concentration of arginase I (ARG I) and the expression of peripheral T-cell receptor ζ chain (TCR ζ) in never smokers, smokers with normal spirometry and COPD patients. Flow cytometry was used to quantify circulating MDSCs and TCR ζ expression. Serum ARG I levels were determined by ELISA. RESULTS: The main findings of this study were that: (1) current smoking upregulates and activates circulating MDSCs both in smoker controls and COPD patients; and, (2) at variance with the smokers with normal spirometry, in patients with COPD this effect persists after quitting smoking and is accompanied by a significant and specific down-regulation of the TCR ζ chain expression in circulating T lymphocytes. CONCLUSION: Smoking modulates circulating MDSCs. Their regulation appears altered in patients with COPD.

EPOC y asma / Chronic obstructive pulmonary disease and asthma

La enfermedad pulmonar obstructiva crónica y el asma son dos enfermedades inflamatorias muy prevalentes,caracterizadas por obstrucción del flujo aéreo, que tienen diferentes mecanismos patogénicos y diferentesgrados de respuesta al tratamiento antiinflamatorio. Sin embargo, en la práctica clínica aparecen con frecuenciapresentaciones clínicas que solapan ambas enfermedades y que no están claramente representadas en losensayos clínicos. Estos pacientes pueden tener una pérdida acelerada de la función pulmonar y un pronósticopeor, por lo que es importante su identificación temprana. Biomarcadores, como la hiperreactividad bronquialo el óxido nítrico en aire exhalado, han mostrado resultados desiguales. Su caracterización fenotípica nospermitiría individualizar y optimizar el tratamiento con corticosteroides inhalados(AU)

Chronic obstructive pulmonary disease and asthma are both highly prevalent inflammatory diseasescharacterized by airway obstruction with distinct pathogenic mechanisms and different degrees of responseto antiinflammatory therapy. However, forms of presentation that show overlap between both diseases andwhich are not clearly represented in clinical trials are frequently encountered in clinical practice. Thesepatients may show accelerated loss of pulmonary function and have a worse prognosis. Therefore their earlyidentification is essential. Biomarkers such as bronchial hyperreactivity or nitric oxide in exhaled air haveyielded discrepant results. Phenotypic characterization will allow treatment with inhaled corticosteroids tobe individually tailored and optimized(AU)

Desaturación en la prueba de marcha de 6 minutos: Su relación con predictores de mortalidad en EPOC / Desaturation during de 6 MWT: Relationship with others outcomes in COPD

Objetivo: La distancia recorrida en la prueba de marcha de 6 minutos (6MWT) predice mortalidad en la Enfermedad pulmonar obstructiva crónica (EPOC) severa. Poco se ha investigado acerca de la desaturación durante la marcha. El objetivo fue determinar la relación entre el Área de desaturación de oxigeno (AD) durante la 6MWT y parámetrossubrogantes de mortalidad como el índice BODE, el VEF1, la disnea, la distancia recorrida en 6MWT y el cociente CI/TLC. Métodos: Se enrolaron 38 pacientes EPOC estables en el Hospital de Clínicas, Buenos Aires.Se midió el VEF1, la distancia y saturación O2 durante la 6MWT, la disnea, el BMI y los volúmenes pulmonares. Se definió AD como la suma de los valores que resultan de restara 100 el número absoluto de saturación en cada minuto. Resultados: Se encontró correlación moderada entre el AD y BODE (r: 0,49) (p : 0,0017), fuerte con el VEF1 (r: - 0,53) (p: 0,0006); con los metros caminados en la 6 MWT fue débil.(r: - 0,33) (p: 0,04). Los pacientes con mayor disnea presentaban mayor AD (r: 0.38) (p: 0.01). Al correlacionar el AD con el CI/TLC se observo una relación moderada (r: -0.36) (p: 0.02).Conclusión: el resultado nos sugiere de manera indirecta un posible rol pronóstico de el AD en la EPOC. Se necesitarán futuros trabajos prospectivos para demostrar dichaasociación con mortalidad, tras la realización de análisis multivariados.

Desaturation during de 6 MWT: Relationship with others outcomes in COPD. Background: The distance walked in a 6-minute walk test (6MWT) predicts mortality in severe Chronic Obstructive Pulmonary Disease (COPD). Little is known about the value ofoxygen desaturation during a 6MWT. The aim of this study was to determine the existence of a relationship between oxygen desaturation area (DA) during the 6MWT and related mortality indicators such as Body-mass index, airflow Obstruction, Dyspnea and Exercise capacity (BODE) index, FEV1, dyspnea, distance walked in the 6MWT and Inspiratory Capacity / Total Lung Capacity (IC/TLC) ratio. Methods: We enrolled 38 patients who met the criteria for stable COPD at the Hospitalde Clinicas, Buenos Aires, Argentina. The observations included the measurement of FEV1, O2 saturation and the distance walked during the 6MWT, the degree of dyspnea, BMI and lung volumes. We defined oxygen desaturation area (DA) as the sum of the values resulting from subtracting from 100 percent the patient’s saturation measurement at each minute of the 6MWT. Results: The correlation between the DA with the BODE index was moderate (r: 0.49) (p: 0.0017), and with FEV1 was strong (r: - 0.53) (p: 0.0006). The correlation with meterswalked in the 6MWT was weak (r: - 0.33) (p: 0.04). Patients with a higher degree of dyspnea have a higher DA (r: 0.38) (p: 0.01). The correlation between the DA and IC/TLC was moderate (r: - 0.36) (p: 0.02).Conclusion: The results of our study suggest a possible indirect prognostic value of the DA in COPD. Prospective studies using multivariate analysis are needed to test association with mortality.

[Chronic obstructive pulmonary disease and asthma]. / EPOC y asma.

Chronic obstructive pulmonary disease and asthma are both highly prevalent inflammatory diseases characterized by airway obstruction with distinct pathogenic mechanisms and different degrees of response to antiinflammatory therapy. However, forms of presentation that show overlap between both diseases and which are not clearly represented in clinical trials are frequently encountered in clinical practice. These patients may show accelerated loss of pulmonary function and have a worse prognosis. Therefore their early identification is essential. Biomarkers such as bronchial hyperreactivity or nitric oxide in exhaled air have yielded discrepant results. Phenotypic characterization will allow treatment with inhaled corticosteroids to be individually tailored and optimized.

Community acquired pneumonia in the tropics.

PURPOSE OF REVIEW: Due to the exponential growth of international exchange, millions of travelers are exposed to respiratory pathogens in the tropics and may return ill. Community-acquired pneumonia is one of the more prevalent infections. RECENT FINDINGS: The acquisition of infections in the tropics, including community-acquired pneumonias, has been described for several centuries. During recent decades some microorganisms have been disclosed as causative of the disease (Legionella pneumophila in 1976 and hantavirus in 1990); other microorganisms are real new pathogens that were not previously demonstrated to have a pathogenic role in humans (e.g. severe acute respiratory syndrome coronavirus producing an outbreak in 2003 and H5N1 avian influenza virus producing an increasing number of human cases over the last few years). SUMMARY: A number of microorganisms may produce pneumonia in people who live or have traveled to tropical zones. History, including geography and epidemiology, physical exam and complementary workout are precious tools for the diagnosis, therapy and prevention. Exposure to microorganisms in tropical areas may show different patterns. A high index of suspicion, detailed investigation of travel, exposure history of the patient, and a basic understanding of the incubation periods and distribution of the various potential pathogens are imperative for the diagnosis.