S100A8/A9 Proteins Mediate Neutrophilic Inflammation and Lung Pathology during Tuberculosis

Rationale: A hallmark of pulmonary tuberculosis (TB) is the formation of granulomas. However, the immune factors that drive the formation of a protective granuloma during latent TB, and the factors that drive the formation of inflammatory granulomas during active TB, are not well defined. Objectives: The objective of this study was to identify the underlying immune mechanisms involved in formation of inflammatory granulomas seen during active TB. Methods: The immune mediators involved in inflammatory granuloma formation during TB were assessed using human samples and experimental models of Mycobacterium tuberculosis infection, using molecular and immunologic techniques. Measurements and Main Results: We demonstrate that in human patients with active TB and in nonhuman primate models of M. tuberculosis infection, neutrophils producing S100 proteins are dominant within the inflammatory lung granulomas seen during active TB. Using the mouse model of TB, we demonstrate that the exacerbated lung inflammation seen as a result of neutrophilic accumulation is dependent on S100A8/A9 proteins. S100A8/A9 proteins promote neutrophil accumulation by inducing production of proinflammatory chemokines and cytokines, and influencing leukocyte trafficking. Importantly, serum levels of S100A8/A9 proteins along with neutrophil-associated chemokines, such as keratinocyte chemoattractant, can be used as potential surrogate biomarkers to assess lung inflammation and disease severity in human TB. Conclusions: Our results thus show a major pathologic role for S100A8/A9 proteins in mediating neutrophil accumulation and inflammation associated with TB. Thus, targeting specific molecules, such as S100A8/A9 proteins, has the potential to decrease lung tissue damage without impacting protective immunity against TB

Desarrollo de un cuestionario para medir los conocimientos del paciente asmático en relación con su enfermedad

Objetivo: Desarrollar un cuestionario en español, autoadministrado, que mida los conocimientos del paciente asmático en relación con su enfermedad y que sea válido, fiable y sensible. Pacientes y métodos: La validez de apariencia y contenido de las preguntas redactadas se estableció por consenso de neumólogos expertos. Para la calificación de la importancia de las preguntas participaron 100 pacientes asmáticos. La reducción del número de preguntas para la versión final del cuestionario se realizó por consenso y tomando en consideración la escala de importancia determinada por los mismos pacientes. Para evaluar la fiabilidad y sensibilidad participaron otros 25 pacientes. El cuestionario se aplicó en 5 ocasiones diferentes: 2 previas y 3 posteriores a la intervención educativa. Se midió la consistencia externa directa e indirecta (índice kappa) y la kappa global. La sensibilidad se determinó con el número de aciertos antes y después de la intervención (prueba de Wilcoxon; p 40%, clínicamente significativo). Resultados: Se redactaron 59 preguntas y la versión final del cuestionario consta de 20. La consistencia directa antes y después de la intervención fue de 0,81-1 en el 76 y el 92% de los casos, respectivamente. El índice kappa antes de la intervención se situó entre 0,41 y 1 en el 96% de los casos, y después fue de 0,81-1 en el 88%. La kappa global antes y después de la intervención fue de 0,12 y 0,43, respectivamente. La mediana de la sensibilidad, medida en porcentaje de cambio, fue del 67% y 10 pacientes mostraron una mejora entre el 81 y el 233%. Conclusiones: El cuestionario es fiable, reúne los criterios de validez de contenido y apariencia y es muy sensible al cambio. En virtud de la magnitud de los resultados, es un instrumento útil para medir los conocimientos del paciente asmático en la práctica clínica o la investigación

Discrepancias entre los datos ofrecidos por la Secretaría de Salud y la Organización Mundial de la Salud sobre tuberculosis en México, 1981-1998 Inconsistencies between reports from the World Health Organization and the Ministry of Health

OBJETIVO: Describir las tendencias de la morbilidad y mortalidad de la tuberculosis en México, entre 1981 y 1998, comparando datos de la Secretaría de Salud y de la Organización Mundial de la Salud. MATERIAL Y MÉTODOS: Se analizó el número de casos y tasas notificados y la tendencia de la enfermedad en los últimos años. Se calculó la incidencia de casos nuevos de tuberculosis bacilíferos mediante el riesgo anual de infección tuberculosa, con lo que se estimó el porcentaje de detección de casos bacilíferos en 1997-1998. RESULTADOS: El número de casos de tuberculosis emitido por la Organización Mundial de la Salud supera al notificado por la Secretaría de Salud, discrepancia que se ha reducido. Los casos bacilíferos se han mantenido entre 1993-1998 y se estimó una detección de 66 y de 26% en 1997 y 1998, respectivamente (para un Riesgo Anual de Infección Tuberculosa de 0.5%). La mortalidad se redujo 6.7% cada año entre 1990 y 1998 mientras que se observó un aumento de casos nuevos, lo que implica la persistencia de la transmisión de la infección entre la población. CONCLUSIONES: Hay discrepancia entre el número de casos de tuberculosis ofrecido por la Secretaría de Salud y la Organización Mundial de la Salud. De acuerdo con las estimaciones por el Riesgo Anual de Infección Tuberculosa se deja de detectar un número considerable de casos bacilíferos.<br>OBJECTIVE: To describe the tuberculosis morbidity and mortality trends in Mexico, by comparing the data reported by the Ministry of Health (MH) and the World Health Organization (WHO) between 1981 and 1998. MATERIAL AND METHODS: The number of cases notified in the past few years, their rates, and the trends of the disease in Mexico were analyzed. The incidence of smear-positive pulmonary tuberculosis was estimated for 1997 and 1998 with the annual tuberculosis infection risk (ATIR), to estimate the percentage of bacilliferous cases in 1997-1998. RESULTS: WHO reported more tuberculosis cases for Mexico than the MH. However, this difference has decreased throughout the years. The notification of smear-positive cases remained stable during 1993-1998. The estimated percentages of detection were 66% for 1997 and 26% for 1998 (based on ATIR of 0.5%). Tuberculosis mortality decreased gradually (6.7% per year) between 1990 and 1998, whereas the number of new cases increased, suggesting the persistence of disease transmission in the population. CONCLUSIONS: Inconsistencies between case notifications from national data and WHO were considerable, but decreased progressively during the study period. According to ATIR estimations, a considerable number of infectious tuberculosis cases are not detected

Discrepancias entre los datos ofrecidos por la Secretaría de Salud y la Organización Mundial de la Salud sobre tuberculosis en México, 1981-1998

Objetivo. Describir las tendencias de la morbilidad y mortalidad de la tuberculosis en México, entre 1981 y 1998, comparando datos de la Secretaría de Salud y de la Organización Mundial de la Salud. Material y métodos. Se analizó el número de casos y tasas notificados y la tendencia de la enfermedad en los últimos años. Se calculó la incidencia de casos nuevos de tuberculosis bacilíferos mediante el riesgo anual de infección tuberculosa, con lo que se estimó el porcentaje de detección de casos bacilíferos en 1997-1998. Resultados. El número de casos de tuberculosis emitido por la Organización Mundial de la Salud supera al notificado por la Secretaría de Salud, discrepancia que se ha reducido. Los casos bacilíferos se han mantenido entre 1993-1998 se estimó una detección de 66 y de 26% en 1997 y 1998, respectivamente (para un Riesgo Anual de Infección Tuberculosa de 0.5%). La mortalidad se redujo 6.7% cada año entre 1990 y 1998 mientras que se observó un aumento de casos nuevos, lo que implica la persistencia de la transmisión de la infección entre la población. Conclusiones. Hay discrepancia entre el número de casos de tuberculosis ofrecido por la Secretaría de Salud y la Organización Mundial de la Salud. De acuerdo con las estimaciones por el Riesgo Anual de Infección Tuberculosa se deja de detectar un número considerable de casos bacilíferos. El texto completo en inglés de este artículo está disponible en: http:// www.insp.mx/salud/index.htm

Modelo predictivo para mortalidad en adultos hospitalizados con neumonía adquirida en la comunidad

Antecedentes: Existe escasa información sobre variables predictoras para mortalidad por neumonía en población mexicana. Objetivo: Identificar un modelo de variables predictoras para mortalidad en adultos hospitalizados por neumonía adquirida en la comunidad (NAC). Método: Estudio de casos y controles de pacientes hospitalizados por NAC. Los casos fueron pacientes con NAC que fallecieron durante la hospitalización y los controles fueron pacientes que no fallecieron. Los pacientes se siguieron durante el tiempo de estudio hasta el egreso o el desenlace de cada uno. La asociación entre las variables independientes (clínicas, índices de gravedad para neumonía) con la variable desenlace (muerte hospitalaria) se evaluó mediante regresión logística. Resultados: Las variables asociadas a mortalidad fueron la edad estratificada de 50-70 años (odds ratio [OR]: 2.35; intervalo de confianza del 95% [IC 95%]: 1.06-5.17) y > 70 años (OR: 2.75; IC 95%: 1.18-6.37), ser mujer (OR: 2.05; IC 95%: 1.11-3.8), antecedente de hipertensión arterial (OR: 0.40; IC 95%: 0.20-0.80), taquicardia (OR: 2.68; IC 95%: 1.16-6.17), taquipnea (OR: 2.85; IC 95%: 1.54-5.29), leucocitos ≥ 12,000 (OR: 2.17; IC 95%: 1.21-3.87) y nitrógeno de la urea >30 mg/dl (OR: 4.85; IC 95%: 2.55-9.24). Conclusiones: El modelo de riesgo que se propone es fácil de documentar con la historia clínica y las pruebas de laboratorio habituales

Accuracy of closed pleural biopsy in the diagnosis of malignant pleural effusion

ABSTRACT Objective: Previous studies have demonstrated that closed pleural biopsy (CPB) has a sensitivity of less than 60% for diagnosing malignancy. Therefore, controversy has recently emerged regarding the value of CPB as a diagnostic test. Our objective was to assess the accuracy of CPB in diagnosing malignancy in patients with pleural effusion. Methods: This was a prospective 8-year study of individuals who underwent CPB to establish the etiology of pleural effusion. Information on each patient was obtained from anatomopathological reports and medical records. When CPB findings showed malignancy or tuberculosis, the biopsy was considered diagnostic, and that was the definitive diagnosis. In cases in which biopsy histopathological findings were nonspecific, a definitive diagnosis was established on the basis of other diagnostic procedures, such as thoracoscopy, thoracotomy, fiberoptic bronchoscopy, biochemical and cellular measurements in pleural fluid, and/or microbiological tests. The accuracy of CPB was determined with 2 × 2 contingency tables. Results: A total of 1034 biopsies from patients with pleural effusion were studied. Of those, 171 (16.54%) were excluded from the accuracy analysis either because of inadequate samples or insufficient information. The results of the accuracy analysis were as follows: sensitivity, 77%; specificity, 98%; positive predictive value, 99%; negative predictive value, 66%; positive likelihood ratio, 38.5; negative likelihood ratio, 0.23; pre-test probability, 2.13; and post-test probability, 82. Conclusions: CPB is useful in clinical practice as a diagnostic test, because there is an important change from pre-test to post-test probability

A novel scoring system to measure radiographic abnormalities and related spirometric values in cured pulmonary tuberculosis.

BACKGROUND: Despite chemotherapy, patients with cured pulmonary tuberculosis may result in lung functional impairment. OBJECTIVE: To evaluate a novel scoring system based on the degree of radiographic abnormalities and related spirometric values in patients with cured pulmonary tuberculosis. METHODS: One hundred and twenty seven patients with cured pulmonary tuberculosis were prospectively enrolled in a referral hospital specializing in respiratory diseases. Spirometry was performed and the extent of radiographic abnormalities was evaluated twice by each of two readers to generate a novel quantitative score. Scoring reproducibility was analyzed by the intra-class correlation coefficient (ICC) and the Bland-Altman method. Multiple linear regression models were performed to assess the association of the extent of radiographic abnormalities with spirometric values. RESULTS: The intra-observer agreement for scoring of radiographic abnormalities (SRA) showed an ICC of 0.81 (CI:95%, 0.67-0.95) and 0.78 (CI:95%, 0.65-0.92), for reader 1 and 2, respectively. Inter-observer reproducibility for the first measurement was 0.83 (CI:95%, 0.71-0.95), and for the second measurement was 0.74 (CI:95%, 0.58-0.90). The Bland-Altman analysis of the intra-observer agreement showed a mean bias of 0.87% and -0.55% and an inter-observer agreement of -0.35% and -1.78%, indicating a minor average systematic variability. After adjustment for age, gender, height, smoking status, pack-years of smoking, and degree of dyspnea, the scoring degree of radiographic abnormalities was significantly and negatively associated with absolute and percent predicted values of FVC: -0.07 (CI:95%, -0.01 to -0.04); -2.48 (CI:95%, -3.45 to -1.50); and FEV1 -0.07 (CI:95%, -0.10 to -0.05); -2.92 (CI:95%, -3.87 to -1.97) respectively, in the patients studied. CONCLUSION: The extent of radiographic abnormalities, as evaluated through our novel scoring system, was inversely associated with spirometric values, and exhibited good reliability and reproducibility. As intra-observer and inter-observer agreement of the SRA varied from good to excellent, the use of SRA in this setting appears acceptable

Association between Highly Active Antiretroviral Therapy and Type of Infectious Respiratory Disease and All-Cause In-Hospital Mortality in Patients with HIV/AIDS: A Case Series

<div><p>Background</p><p>Respiratory manifestations of HIV disease differ globally due to differences in current availability of effective highly active antiretroviral therapy (HAART) programs and epidemiology of infectious diseases.</p><p>Objective</p><p>To describe the association between HAART and discharge diagnosis and all-cause in-hospital mortality among hospitalized patients with infectious respiratory disease and HIV/AIDS.</p><p>Material and Methods</p><p>We retrospectively reviewed the records of patients hospitalized at a specialty hospital for respiratory diseases in Mexico City between January 1st, 2010 and December 31st, 2011. We included patients whose discharge diagnosis included HIV or AIDS and at least one infectious respiratory diagnosis. The information source was the clinical chart. We analyzed the association between HAART for 180 days or more and type of respiratory disease using polytomous logistic regression and all-cause hospital mortality by multiple logistic regressions.</p><p>Results</p><p>We studied 308 patients, of whom 206 (66.9%) had been diagnosed with HIV infection before admission to the hospital. The CD4+ lymphocyte median count was 68 cells/mm³ [interquartile range (IQR): 30–150]. Seventy-five (24.4%) cases had received HAART for more than 180 days. <i>Pneumocystis jirovecii</i> pneumonia (PJP) (n = 142), tuberculosis (n = 63), and bacterial community-acquired pneumonia (n = 60) were the most frequent discharge diagnoses. Receiving HAART for more than 180 days was associated with a lower probability of PJP [Adjusted odd ratio (aOR): 0.245, 95% Confidence Interval (CI): 0.08–0.8, p = 0.02], adjusted for sociodemographic and clinical covariates. HAART was independently associated with reduced odds (aOR 0.214, 95% CI 0.06–0.75) of all-cause in-hospital mortality, adjusting for HIV diagnosis previous to hospitalization, age, access to social security, low socioeconomic level, CD4 cell count, viral load, and discharge diagnoses.</p><p>Conclusions</p><p>HAART for 180 days or more was associated with 79% decrease in all-cause in-hospital mortality and lower frequency of PJP as discharge diagnosis. The prevalence of poorly controlled HIV was high, regardless of whether HIV was diagnosed before or during admission. HIV diagnosis and treatment resources should be improved, and strengthening of HAART program needs to be promoted.</p></div

Bland-Altman plot of measurement differences against measurements averages with 95% limits of agreement superimposed for pair-wise comparisons of Scoring of radiographic abnormalities (SRA), for inter-observer agreement: A) between reader 1 vs reader 2 for the first measurement, B) between reader one vs reader two for the second measurement.

<p>Bland-Altman plot of measurement differences against measurements averages with 95% limits of agreement superimposed for pair-wise comparisons of Scoring of radiographic abnormalities (SRA), for inter-observer agreement: A) between reader 1 vs reader 2 for the first measurement, B) between reader one vs reader two for the second measurement.</p

Bland-Altman plot of measurement differences against measurements average with a 95% limit of agreement superimposed for pair-wise comparisons of scoring of radiographic abnormalities (SRA), for intra-observer agreement: A) between reader one for the first and second measurements, B) between reader two for the first and second measurements.

<p>Bland-Altman plot of measurement differences against measurements average with a 95% limit of agreement superimposed for pair-wise comparisons of scoring of radiographic abnormalities (SRA), for intra-observer agreement: A) between reader one for the first and second measurements, B) between reader two for the first and second measurements.</p